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Previous Volume 329:909-914 September 23, 1993 Number 13 Next

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ABSTRACT

Background Translocations involving chromosome band 11q23 are very frequent in both acute lymphoblastic and acute myeloid leukemias and are the most common genetic alteration in infants with leukemia. In all age groups and all phenotypes of leukemia, an 11q23 translocation carries a poor prognosis. A major question has been whether one or several genes on band 11q23 are implicated in these leukemias. Previously, we identified the chromosomal breakpoint region in leukemias with the common 11q23 translocations and subsequently cloned a gene named MLL that spans the 11q23 breakpoint.

Methods We isolated a 0.74-kb BamHI fragment from a complementary DNA (cDNA) clone of the MLL gene. To determine the incidence of MLL rearrangements in patients with 11q23 abnormalities, we analyzed DNA from 61 patients with acute leukemia, 3 cell lines derived from such patients, and 20 patients with non-Hodgkin's lymphoma and 11q23 aberrations.

Results The 0.74-kb cDNA probe detected DNA rearrangements in the MLL gene in 58 of the patients with leukemia, in the 3 cell lines, and in 3 of the patients with lymphoma. All the breaks occurred in an 8.3-kb breakpoint cluster region within the MLL gene. The probe identified DNA rearrangements in all 48 patients with the five common 11q23 translocations involving chromosomes 4, 6, 9, and 19, as well as in 16 patients with uncommon 11q23 aberrations. Twenty-one different chromosomal breakpoints involving the MLL gene were detected.

Conclusions MLL gene rearrangements were detected with a single probe and a single restriction-enzyme digest in all DNA samples from patients with the common 11q23 translocations as well as in 16 patients or cell lines with other 11q23 anomalies. The ability to detect an MLL gene rearrangement rapidly and reliably, especially in patients with limited material for cytogenetic analysis, should make it possible to identify patients who have a poor prognosis and therefore require aggressive chemotherapy or marrow transplantation.

Translocations involving the chromosome band 11q23 occur frequently in hematologic cancers, affecting 7 to 10 percent of acute lymphoblastic leukemias (ALLs), with the (4;11) and (11;19) translocations predominating, and 5 to 6 percent of AMLs, with the (6;11), (9;11), and (11;19) translocations being the most common^4,5,6,7,8. Translocations involving 11q23 are the single most common cytogenetic abnormality in infants with acute leukemia, regardless of the phenotype^9,10. They account for approximately 70 percent of all cases of both AML and ALL in infants. These translocations are also observed in therapy-related leukemias, especially in patients previously treated with inhibitors of topoisomerase II. Flow cytometry may reveal the expression of myeloid or monocytoid markers in addition to B-cell lymphoid markers in patients with ALL¹¹. Typically, patients with AML have acute myelomonocytic leukemia (AML-M4) or acute monoblastic leukemia (AML-M5), and they may express lymphoid markers in addition to myeloid markers^12,13. These observations suggest that rearrangements of a gene at 11q23 may affect a pluripotential progenitor cell that is capable of either myeloid or lymphoid differentiation. Alternatively, a mechanism for differentiation that is shared by both lymphoid and myelomonocytic stem cells may be deregulated as a consequence of these translocations.

Patients with AML and ALL who have 11q23 translocations have aggressive clinical features and often present with hyperleukocytosis and early involvement of the central nervous system. An 11q23 translocation in both AML and ALL confers a very poor prognosis. In the report of the Sixth International Workshop on Chromosomes in Leukemia, there were no long-term survivors among patients with ALL and the (4;11) translocation, whereas patients with AML and translocations involving 11q had a long-term disease-free survival rate of 3 percent¹⁴. Thus, the detection of the gene involved in these translocations might be the critical first step in identifying patients who require intensive therapy and designing new treatment strategies based on the molecular genetic consequences of these translocations.

We identified a yeast artificial chromosome that contained the breakpoint region in leukemias with several common 11q23 translocations¹⁵. Subsequently, we cloned a gene named MLL (for mixed-lineage leukemia or myeloid-lymphoid leukemia) that spans the breakpoint on 11q23¹⁶. Several groups have cloned and sequenced the same gene and have called it Htrx, ALL-1, and HRX^17,18,19. The strong homology between the zinc-finger region of MLL and the Drosophila trithorax gene suggests that the MLL gene has been evolutionarily conserved. The MLL gene has multiple large transcripts in the range of 13 to 15 kb and is transcribed in a centromere-to-telomere direction²⁰. The involved genes on chromosomes 4 and 19 have been identified; the translocations with 11q23 in these patients result in fusion transcripts^18,19.

A major question in the analysis of leukemias with 11q23 aberrations is whether a single oncogene or a group of oncogenes is involved in each translocation subtype and whether there is heterogeneity among the common subtypes. In addition, a large number of rare translocations involving 11q23 have been identified, but their relation to the common 11q23 translocations has not been determined. We have identified a single complementary DNA (cDNA) probe from the MLL gene that could detect rearrangements in DNA digested with a single enzyme from all leukemias with the common 11q23 translocations, as well as those with rare chromosomal anomalies with a breakpoint at band 11q23.

Methods

Patients and Cell Lines

Samples of bone marrow, lymph nodes, or peripheral blood were obtained at the University of Chicago Medical Center, Saitama Cancer Center, Southwest Biomedical Research Institute, and Memorial Sloan-Kettering Cancer Center. Samples from 61 patients with acute leukemia and 20 patients with lymphoma were selected on the basis of a karyotype containing an 11q23 abnormality and the availability of cryopreserved samples of leukemic bone marrow or peripheral blood. In the patients with lymphoma, cytogenetic and molecular analyses were performed on lymph-node samples.

The DNA from three cell lines was also analyzed. The cell line RS4;11 was derived from a patient with B-cell ALL and was a gift from J. Kersey, University of Minnesota²¹; SUP-T13 was derived from a patient with T-cell ALL and was a gift from S. Smith, University of Chicago²²; and Karpas 45 was derived from a patient with T-cell ALL and was a gift from A. Karpas, Cambridge University²³.

Cytogenetic Analysis

Cytogenetic analysis was performed with a trypsin-Giemsa banding technique. Chromosomal abnormalities were described according to the International System for Human Cytogenetic Nomenclature²⁴. Fluorescence in situ hybridization was performed as previously described¹⁵.

cDNA Library

A cDNA library was prepared from a monocytic cell line as described by McCabe et al²⁰. The library was screened with probes from the centromeric and telomeric ends of a 14-kb genomic fragment of BamHI (clone 14), and several cDNA clones were obtained and mapped with restriction endonucleases.

Molecular Analysis

DNA was extracted from cryopreserved cells and digested with restriction enzymes, subjected to electrophoresis on 0.7 percent agarose gels, transferred to nylon membranes, and hybridized with radiolabeled cDNA probes at 42 °C. All DNA blots were washed in 1 x saline sodium citrate buffer (0.15 M sodium chloride, 0.015 M sodium citrate) and 1 percent sodium dodecyl sulfate at 65 °C before autoradiography was performed.

Results

We isolated a 0.74-kb BamHI fragment from a cDNA subclone of MLL. This fragment was composed of exons located at the centromeric and telomeric ends of an 8.3-kb genomic BamHI fragment of the MLL gene as well as exons dispersed along the genomic fragment (Figure 1). We detected rearrangements of the MLL gene on Southern blot analysis in 61 patients (58 with leukemia and 3 with lymphoma) and 3 cell lines by using the 0.74-kb cDNA fragment as a probe (Figure 2). The probe identified rearrangements in all 48 samples of DNA (from 46 patients and 2 cell lines) with the common translocations involving 11q23 (Table 1). We also identified similar MLL gene rearrangements in DNA from 10 patients and 1 cell line with several less common 11q23 translocations listed by Mitelman et al.^25,26 as well as from 5 other patients with 11q23 anomalies not reported by Mitelman et al (Table 2). Rearrangements were detected in the three cell lines with 11q23 translocations -- RS4;11, SUP-T13, and Karpas 45. In approximately 75 percent of patients with DNA rearrangements, two rearranged bands were identified, and in 25 percent only one rearranged band was present. The probe did not detect rearrangements in samples from patients in remission who had rearrangements in the DNA from their leukemic cells. In addition, rearrangements were not identified in three patients with rare 11q23 translocations involving chromosome bands 4q23, 5q13, and 10p13. Two of these three patients and several of the patients with lymphoma have recently been studied with fluorescence in situ hybridization and were found to have breakpoints on 11q23 far from the MLL gene²⁷.

View larger version (17K): [in this window] [in a new window]   Figure 1. The Breakpoint Cluster Region of the MLL Gene.qc Panel A shows the overview restriction-enzyme map of a region of chromosome band 11q23 subcloned in yeast artificial chromosome YB22B215. MLL sequences have previously been identified within the 92-kb NotI fragment. Panel B shows the position of the breakpoint cluster region and its relation to the overview map. Panel C shows a restriction-enzyme map of the 4.1-kb cDNA clone 14P18B. The shaded area represents the 0.74-kb BamHI probe. P denotes PstI, H HindIII, and E EcoRI.

 

View larger version (139K): [in this window] [in a new window]   Figure 2. Results of Southern Blotting of DNA from Patients with AML, ALL, or Lymphoma. The DNA was digested with BamHI and then probed with the 0.74-kb BamHI cDNA fragment. The DNA rearrangements are indicated by the arrows. Lane 1 contains DNA from normal peripheral-blood white cells; lane 2, AML DNA with t(1;11)(q21;q23); lanes 3, 4, 5, 6, and 7, ALL DNA with t(4;11)(q21;q23); lanes 8 and 9, AML DNA with t(6;11)(q27;q23); lane 10, AML DNA with t(9;11)(p22;q23); lane 11, AML DNA with t(10;11)(p13;q21); lane 12, lymphoma DNA with t(10;11)(p15;q22); lane 13, AML DNA with ins(10;11)(p11;q23q24); lane 14, AML DNA with ins(10;11)(p13;q21q24); lane 15, ALL DNA with t(11;19)(q23;p13.3); lane 16, AML DNA with t(11;19)(q23;p13.3); and lane 17, AML DNA with t(11;22)(q23;q12). A single germline band was detected in normal DNA in lane 1 and in DNA samples from patients with non-11q23 breakpoints in lanes 11, 12, and 14. Rearrangements were detected in all the other samples. The samples in lanes 2, 3, 4, 6, 7, 8, 10, 13, 16, and 17 had two rearranged bands, and the samples in lanes 5, 9, and 15 had one rearranged band.

 

View this table: [in this window] [in a new window]   Table 1. DNA Rearrangements Detected with the 0.74-kb cDNA Probe in 46 Patients with Leukemia and Common 11q23 Translocations.

 

View this table: [in this window] [in a new window]   Table 2. DNA Rearrangements Detected with the 0.74-kb cDNA Probe in 12 Patients with Leukemia and 1 Leukemic Cell Line with Uncommon 11q23 Aberrations.

 
The age distribution of the patients with leukemia in whom DNA rearrangements were detected was broad: 11 patients were 1 year old or younger, 16 were 2 to 16 years of age, and 31 were 17 years of age or older. There were 27 female and 31 male patients. The samples from the 28 patients with ALL and 30 with AML were indistinguishable on Southern blot analysis with the use of our probe.

We also examined 20 patients with non-Hodgkin's lymphoma and detected rearrangements in 3: 1 with follicular small-cleaved-cell lymphoma, 1 with Burkitt's lymphoma, and 1 with a diffuse mixed-cell lymphoma (Table 3). In addition to an 11q23 aberration, the patients with follicular lymphoma and Burkitt's lymphoma also had the cytogenetic abnormalities that are characteristic of these diseases (Table 3). The other 17 patients with lymphoma and 11q23 abnormalities, primarily deletions and duplications, had no rearrangements identified by our cDNA probe, presumably because the breakpoints did not involve MLL.

View this table: [in this window] [in a new window]   Table 3. DNA Rearrangements Detected with the 0.74-kb cDNA Probe in Three Patients with Non-Hodgkin's Lymphoma with 11q23 Anomalies.

 
Discussion

Although it has long been recognized that there are a variety of recurring 11q23 aberrations in leukemia and lymphoma, the specific location of these breakpoints has not been identified. A major question has been whether one or several oncogenes might be implicated in the pathogenesis of these hematologic cancers, given their diverse phenotypes and multiple translocation partners. Previous investigators have reported conflicting results because of the unavailability of specific DNA probes^28,29. Because chromosome band 11q23 contains approximately 10,000 kb of DNA, the clarification of this issue has required the use of techniques that permit increasing precision in the localization of breakpoints^{30,31,32,33,34,35,36}.

We have previously used fluorescence in situ hybridization to localize the breakpoint of the common 11q23 translocations to a region of 330 kb. In the current study, we used Southern blot analysis to provide evidence that all the leukemias with the common 11q23 translocations and the majority with rare aberrations involve the rearrangement of a single, recently identified gene, MLL. Thus, MLL is one of the oncogenes most frequently involved in hematologic cancers.

We identified DNA rearrangements in 61 patients and 3 cell lines with 11q23 abnormalities and delineated an 8.3-kb breakpoint cluster region within the MLL gene by using a 0.74-kb BamHI cDNA fragment as a probe. The probe identified DNA rearrangements in all patients with the common translocations as well as in 16 with less common aberrations. No heterogeneity was detectable on Southern blot analysis within each cytogenetic subtype or among the different subtypes of 11q23 translocations. Using the probe, we also identified three patients with lymphoma who had the same breakpoint as the patients with leukemia and common 11q23 translocations.

In molecular diagnostic studies of cancer, multiple probes and several enzyme digests are often necessary to establish or rule out the involvement of a specific oncogene. In this study, we found that the use of a single probe and a single enzyme digest was sufficient to detect all MLL gene rearrangements, an important point in patients with limited material for cytogenetic analysis. Moreover, recent studies have shown a higher rate of detection of gene rearrangements, such as the Philadelphia chromosome, with molecular probes than with cytogenetic methods³⁷.

Cytogenetic and molecular genetic analyses of leukemias are often critical in establishing a diagnosis that can be used to select specific therapy. For example, in acute promyelocytic leukemia, which is characterized by the (15;17) translocation, the use of all-trans-retinoic acid has led to a high rate of complete remission³⁸. Because patients with leukemia with 11q23 translocations have an extremely poor prognosis with standard treatment regimens, the ability to detect an MLL gene rearrangement might allow the identification of patients who would benefit from more aggressive therapy. This is likely to be particularly important in infants with leukemia, because 70 percent have a rearrangement of the MLL gene, whether or not an 11q23 translocation is detected on cytogenetic analysis³⁹. Current protocols have adopted the approach of stratifying patients to treatment regimens on the basis of cytogenetic or molecular genetic criteria⁴⁰. Patients with a high risk of relapse, such as those with MLL gene rearrangements, may be advised to undergo intensive chemotherapy and allogeneic bone marrow transplantation.

The spectrum of diseases that involve the MLL gene is unique among hematologic cancers in that rearrangements of the same gene have been identified in ALL and AML as well as in low- and high-grade non-Hodgkin's lymphomas. In hematologic cancers, translocations that lead to the formation of chimeric genes are usually limited to one partner; for example, BCR and ABL are only involved in the (9;22) translocation in chronic myelogenous leukemia. Rarely, alternative translocation partners have been identified; the (8;21) and (3;21) translocations have both been found to generate fusion genes involving the AML1 gene on chromosome 21⁴¹. Remarkably, we identified 21 different chromosomal regions associated with MLL in 11q23 aberrations. This exceeds the number of different genetic partners, identified over the past 20 years, that involve the immunoglobulin and T-cell-receptor genes. The identification of MLL gene rearrangements represents an important step in the isolation of a series of new genes involved in these leukemias and lymphomas.

Cimino et al. have described a 0.48-kb DdeI genomic fragment that detected rearrangements in a 5.8-kb region in 26 of 30 patients (87 percent) with the (4;11), (9;11), and (11;19) translocations^42,43. They hypothesized that the breaks in the DNA from the other four patients, which were not identified by the probe, occurred either at another site within the gene or at other loci in 11q23. The breakpoint cluster region that we identified encompasses a slightly larger region of 8.3 kb and contains the breakpoints in all leukemias with the common translocations as well as many with rare translocations.

Although the majority of 11q23 translocations involve MLL, molecular studies showed that the 11q23 band contains breakpoints for at least three other cancer-related translocations. Studies of the RCK8 B-cell lymphoma line have led to the identification of a gene called RCK that is 300 kb telomeric to MLL^44,45. In addition, we cloned an 11q23 translocation from a patient with a null-cell ALL whose breakpoint is also telomeric to MLL and RCK⁴⁶. Recently, the PLZF gene, cloned from a patient with acute promyelocytic leukemia and a variant (11;17) translocation, was shown to be centromeric to MLL^27,47.

The MLL gene appears to be critically involved in leukemia and lymphoma. The 0.74-kb cDNA probe should be useful in cloning the breakpoints of cancers that involve MLL, in the identification of new genes, and in further molecular analysis of these translocations. This probe may also have broad clinical application, since all gene rearrangements can be detected with a single probe and a single enzyme digest. This probe may also be of value in monitoring the response to chemotherapy and assessing residual disease after treatment. In both childhood and adult leukemias, this may allow earlier detection of a high-risk group that requires aggressive treatment.

Supported in part by grants from the National Institutes of Health (CA42557 to Dr. Rowley; CA40046 to Drs. Larson, Le Beau, and Rowley; CA38725 to Dr. Diaz; and CA34775 to Dr. Chaganti), a grant from the Department of Energy (DE-FG02-86ER60408 to Dr. Rowley), a grant from the Spastic Paralysis Research Foundation, Illinois-Eastern Iowa District of Kiwanis International (to Drs. Rowley and Diaz), a National Cancer Institute Environmental Carcinogenesis Training Grant (5T32 CA09273-12 to Dr. Burnett), and a Basic Research Training in Medical Oncology Grant (5T32CA09566 to Dr. Thirman). Dr. Le Beau is a Scholar of the Leukemia Society of America. Dr. Thirman is a recipient of a Young Investigator Award from the American Society of Clinical Oncology.

We are indebted to Paul Gardner, Rafael Espinosa III, and Elizabeth van Melle for their technical assistance.

Source Information

From the Section of Hematology and Oncology, Departments of Medicine (M.J.T., R.C.B., D.M., H.K., R.A.L., M.M.L., M.O.D., J.D.R.), Molecular Genetics and Cell Biology (H.J.G., S.Z.P., J.D.R.), and Pediatrics (N.R.M.), University of Chicago, Chicago; the Saitama Cancer Center, Saitama, Japan (Y.K.); Southwest Biomedical Research Institute and Genetrix, Inc., Scottsdale, Ariz. (R.M., A.A.S.); and Memorial Sloan-Kettering Cancer Center, New York (R.S.K.C.).Presented in part at the annual meeting of the American Society of Hematology, Anaheim, Calif., December 4-8, 1992.

References

1. Rowley JD. Molecular cytogenetics: Rosetta stone for understanding cancer -- twenty-ninth G.H.A. Clowes memorial award lecture. Cancer Res 1990;50:3816-3825. [Free Full Text]
2. Rowley JD. Recurring chromosome abnormalities in leukemia and lymphoma. Semin Hematol 1990;27:122-136. [Medline]
3. Nichols J, Nimer SD. Transcription factors, translocations, and leukemia. Blood 1992;80:2953-2963. [Free Full Text]
4. Sandberg AA. The chromosomes in human cancer and leukemia. 2nd ed. New York: Elsevier, 1990.
5. Pui C-H, Frankel LS, Carroll AJ, et al. Clinical characteristics and treatment outcome of childhood acute lymphoblastic leukemia with the t(4;11)(q21;q23): a collaborative study of 40 cases. Blood 1991;77:440-447. [Free Full Text]
6. Arthur DC, Bloomfield CD, Lindquist LL, Nesbit ME Jr. Translocation 4;11 in acute lymphoblastic leukemia: clinical characteristics and prognostic significance. Blood 1982;59:96-99. [Free Full Text]
7. Fourth International Workshop on Chromosomes in Leukemia 1982: clinical significance of chromosomal abnormalities in acute nonlymphoblastic leukemia. Cancer Genet Cytogenet 1984;11:332-350. [Medline]
8. Huret JL, Brizard A, Slater R, et al. Cytogenetic heterogeneity in t(11;19) acute leukemia: clinical, hematological and cytogenetic analyses of 48 patients -- updated published cases and 16 new observations. Leukemia 1993;7:152-160. [Medline]
9. Kaneko Y, Shikano T, Maseki N, et al. Clinical characteristics of infant acute leukemia with or without 11q23 translocations. Leukemia 1988;2:672-676. [Medline]
10. Gibbons B, Katz FE, Ganly P, Chessells JM. Infant acute lymphoblastic leukaemia with t(11;19). Br J Haematol 1990;74:264-269. [Medline]
11. Drexler HG, Thiel E, Ludwig W-D. Review of the incidence and clinical relevance of myeloid antigen-positive acute lymphoblastic leukemia. Leukemia 1991;5:637-645. [Medline]
12. Cuneo A, Michaux JL, Ferrant A, et al. Correlation of cytogenetic patterns and clinicobiological features in adult acute myeloid leukemia expressing lymphoid markers. Blood 1992;79:720-727. [Free Full Text]
13. Hudson MM, Raimondi SC, Behm FG, Pui C-H. Childhood acute leukemia with t(11;19) (q23;p13). Leukemia 1991;5:1064-1068. [Medline]
14. Sixth International Workshop on Chromosomes in Leukemia: London, England, May 11-18, 1987: selected papers. Cancer Genet Cytogenet 1989;40:171-216. [CrossRef][Medline]
15. Rowley JD, Diaz MO, Espinosa R III, et al. Mapping chromosome band 11q23 in human acute leukemia with biotinylated probes: identification of 11q23 translocation breakpoints with a yeast artificial chromosome. Proc Natl Acad Sci U S A 1990;87:9358-9362. [Free Full Text]
16. Ziemin van der Poel S, McCabe NR, Gill HJ, et al. Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias. Proc Natl Acad Sci U S A 1991;88:10735-10739. [Erratum, Proc Natl Acad Sci U S A 1992;89:4220.] [Free Full Text]
17. Djabali M, Selleri L, Parry P, Bower M, Young BD, Evans GA. A trithorax-like gene is interrupted by chromosome 11q23 translocations in acute leukaemias. Nat Genet 1992;2:113-118. [CrossRef][Medline]
18. Gu Y, Nakamura T, Alder H, et al. The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene. Cell 1992;71:701-708. [CrossRef][Medline]
19. Tkachuk DC, Kohler S, Cleary ML. Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias. Cell 1992;71:691-700. [CrossRef][Medline]
20. McCabe NR, Burnett RC, Gill HJ, et al. Cloning of cDNAs of the MLL gene that detect DNA rearrangements and altered RNA transcripts in human leukemic cells with 11q23 translocations. Proc Natl Acad Sci U S A 1992;89:11794-11798. [Free Full Text]
21. Stong RC, Kersey JH. In vitro culture of leukemic cells in t(4;11) acute leukemia. Blood 1985;66:439-443. [Free Full Text]
22. Smith SD, McFall P, Morgan R, et al. Long-term growth of malignant thymocytes in vitro. Blood 1989;73:2182-2187. [Free Full Text]
23. Karpas A, Hayhoe FGJ, Greenberger JS, et al. The establishment and cytological, cytochemical and immunological characterisation of human haemic cell lines: evidence for heterogeneity. Leuk Res 1977;1:35-49.
24. Mitelman F, ed. ISCN guideline for cancer cytogenetics. Supplement to: An international system for human cytogenetic nomenclature VI. Basel, Switzerland: S. Karger, 1991.
25. Mitelman F, Kaneko Y, Trent J. Report of the committee on chromosome changes in neoplasia. Cytogenet Cell Genet 1991;58:1053-1079. 
26. Mitelman F. Catalog of chromosome aberrations in cancer. 4th ed. New York: Wiley-Liss, 1991.
27. Kobayashi H, Espinosa R III, Thirman MJ, et al. Heterogeneity of breakpoints of 11q23 in hematologic malignancies identified with fluorescence in situ hybridization. Blood 1993;82:547-551. [Free Full Text]
28. Cherif D, Der-Sarkissian H, Derre J, Tokino T, Nakamura Y, Berger R. The 11q23 breakpoint in acute leukemia with t(11;19) (q23;p13) is distal to those of t(4;11), t(6;11) and t(9;11). Genes Chromosomes Cancer 1992;4:107-112. [Medline]
29. Cotter FE, Lillington D, Hampton G, et al. Gene mapping by microdissection and enzymatic amplification: heterogeneity in leukaemia associated breakpoints on chromosome 11. Genes Chromosomes Cancer 1991;3:8-15. [Medline]
30. Savage PD, Jones C, Silver J, et al. Mapping studies and expression of genes located on human chromosome 11, band q23. Cytogenet Cell Genet 1988;49:289-292. [Medline]
31. Yunis JJ, Jones C, Madden MT, Lu D, Mayer MG. Gene order, amplification, and rearrangement of chromosome band 11q23 in hematologic malignancies. Genomics 1989;5:84-90. [CrossRef][Medline]
32. Tunnacliffe A, McGuire RS. A physical linkage group in human chromosome band 11q23 covering a region implicated in leukocyte neoplasia. Genomics 1990;8:447-453. [Medline]
33. Savage PD, Shapiro M, Langdon WY, et al. Relationship of the human protooncogene CBL2 on 11q23 to the t(4;11), t(11;22), and t(11;14) breakpoints. Cytogenet Cell Genet 1991;56:112-115. [Medline]
34. Das S, Cotter FE, Gibbons B, Dhut S, Young BD. CD3G is within 200 kb of the leukemic t(4;11) translocation breakpoint. Genes Chromosomes Cancer 1991;3:44-47. [Medline]
35. Chen C-S, Medberry PS, Arthur DC, Kersey JH. Breakpoint clustering in t(4;11)(q21;q23) acute leukemia. Blood 1991;78:2498-2504. [Free Full Text]
36. Radice P, Tunnacliffe A. Distinct breakpoints in band 11q23 of the t(4;11) and t(11;14) associated with leukocyte malignancy. Genes Chromosomes Cancer 1992;5:50-56. [Medline]
37. Westbrook CA, Hooberman AL, Spino C, et al. Clinical significance of the BCR-ABL fusion gene in adult lymphoblastic leukemia: a Cancer and Leukemia Group B Study (8762). Blood 1992;80:2983-2990. [Free Full Text]
38. Fenaux P, Castaigne S, Dombret H, et al. All-transretinoic acid followed by intensive chemotherapy gives a high complete remission rate and may prolong remissions in newly diagnosed acute promyelocytic leukemia: a pilot study on 26 cases. Blood 1992;80:2176-2181. [Free Full Text]
39. Chen C-S, Sorensen PH, Domer PH, et al. Molecular rearrangements on chromosome 11q23 predominate in infant acute lymphoblastic leukemia and are associated with specific biologic variables and poor outcome. Blood 1993;81:2386-2393. [Free Full Text]
40. Bloomfield CD. Prognostic factors for selecting curative therapy for adult acute myeloid leukemia. Leukemia 1992;6:Suppl 4:65-67.
41. Nucifora G, Birn DJ, Espinosa R III, et al. Involvement of the AML1 gene in the t(3;21) in therapy-related leukemia and in chronic myeloid leukemia in blast crisis. Blood 1993;81:2728-2734. [Free Full Text]
42. Cimino G, Moir DT, Canaani O, et al. Cloning of ALL-1, the locus involved in leukemias with the t(4;11)(q21;q23), t(9;11)(p22;q23), and t(11;19)(q23;p13) chromosome translocations. Cancer Res 1991;51:6712-6714. [Free Full Text]
43. Cimino G, Nakamura T, Gu Y, et al. An altered 11-kilobase transcript in leukemic cell lines with the t(4;11)(q21;q23) chromosome translocation. Cancer Res 1992;52:3811-3813. [Free Full Text]
44. Akao Y, Tsujimoto Y, Finan J, Nowell PC, Croce CM. Molecular characterization of a t(11;14)(q23;q32) chromosome translocation in a B-cell lymphoma. Cancer Res 1990;50:4856-4859. [Free Full Text]
45. Akao Y, Seto M, Takahashi T, et al. Molecular cloning of the chromosomal breakpoint of a B-cell lymphoma with the t(11;14)(q23;q32) translocation. Cancer Res 1991;51:1574-1576. [Free Full Text]
46. Burnett RC, Espinosa R III, Shows TB, et al. Molecular analysis of a t(11;14)(q23;q11) from a patient with null-cell acute lymphoblastic leukemia. Genes Chromosomes Cancer 1993;7:38-46. [Medline]
47. Chen Z, Brand NJ, Chen A, et al. Fusion between a novel Kruppel-like zinc finger gene and the retinoic acid receptor-alpha locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia. EMBO J 1993;12:1161-1167. [Medline]

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• Li, Z., Luo, R. T., Mi, S., Sun, M., Chen, P., Bao, J., Neilly, M. B., Jayathilaka, N., Johnson, D. S., Wang, L., Lavau, C., Zhang, Y., Tseng, C., Zhang, X., Wang, J., Yu, J., Yang, H., Wang, S. M., Rowley, J. D., Chen, J., Thirman, M. J. (2009). Consistent Deregulation of Gene Expression between Human and Murine MLL Rearrangement Leukemias. Cancer Res. 69: 1109-1116 [Abstract] [Full Text]  
• Harper, D. P., Aplan, P. D. (2008). Chromosomal Rearrangements Leading to MLL Gene Fusions: Clinical and Biological Aspects. Cancer Res. 68: 10024-10027 [Abstract] [Full Text]  
• Liu, H., Cheng, E. H.-Y., Hsieh, J. J.-D. (2007). Bimodal degradation of MLL by SCFSkp2 and APCCdc20 assures cell cycle execution: a critical regulatory circuit lost in leukemogenic MLL fusions. Genes Dev. 21: 2385-2398 [Abstract] [Full Text]  
• Wolff, D. J., Bagg, A., Cooley, L. D., Dewald, G. W., Hirsch, B. A., Jacky, P. B., Rao, K. W., Rao, P. N., the Association for Molecular Pathology Clinical P, (2007). Guidance for Fluorescence in Situ Hybridization Testing in Hematologic Disorders. J. Mol. Diagn. 9: 134-143 [Abstract] [Full Text]  
• Erdman, J. W. Jr., Balentine, D., Arab, L., Beecher, G., Dwyer, J. T., Folts, J., Harnly, J., Hollman, P., Keen, C. L., Mazza, G., Messina, M., Scalbert, A., Vita, J., Williamson, G., Burrowes, J. (2007). Flavonoids and Heart Health: Proceedings of the ILSI North America Flavonoids Workshop, May 31-June 1, 2005, Washington, DC. J. Nutr. 137: 718S-737S [Abstract] [Full Text]  
• Santillan, D. A., Theisler, C. M., Ryan, A. S., Popovic, R., Stuart, T., Zhou, M.-M., Alkan, S., Zeleznik-Le, N. J. (2006). Bromodomain and Histone Acetyltransferase Domain Specificities Control Mixed Lineage Leukemia Phenotype.. Cancer Res. 66: 10032-10039 [Abstract] [Full Text]  
• Moneypenny, C. G., Shao, J., Song, Y., Gallagher, E. P. (2006). MLL rearrangements are induced by low doses of etoposide in human fetal hematopoietic stem cells. Carcinogenesis 27: 874-881 [Abstract] [Full Text]  
• Libura, J., Slater, D. J., Felix, C. A., Richardson, C. (2005). Therapy-related acute myeloid leukemia-like MLL rearrangements are induced by etoposide in primary human CD34+ cells and remain stable after clonal expansion. Blood 105: 2124-2131 [Abstract] [Full Text]  
• Pagano, L., Pulsoni, A., Vignetti, M., Tosti, M. E., Falcucci, P., Fazi, P., Fianchi, L., Levis, A., Bosi, A., Angelucci, E., Bregni, M., Gabbas, A., Peta, A., Coser, P., Ricciuti, F., Morselli, M., Caira, M., Foa, R., Amadori, S., Mandelli, F., Leone, G., On behalf of GIMEMA, (2005). Secondary acute myeloid leukaemia: results of conventional treatments. Experience of GIMEMA trials. Ann Oncol 16: 228-233 [Abstract] [Full Text]  
• Tallman, M. S., Kim, H. T., Paietta, E., Bennett, J. M., Dewald, G., Cassileth, P. A., Wiernik, P. H., Rowe, J. M. (2004). Acute Monocytic Leukemia (French-American-British classification M5) Does Not Have a Worse Prognosis Than Other Subtypes of Acute Myeloid Leukemia: A Report From the Eastern Cooperative Oncology Group. JCO 22: 1276-1286 [Abstract] [Full Text]  
• Audouin, J., Comperat, E., Tourneau, A. L., Camilleri-Broet, S., Adida, C., Molina, T., Diebold, J. (2003). Myeloid Sarcoma: Clinical and Morphologic Criteria Useful for Diagnosis. INT J SURG PATHOL 11: 271-282 [Abstract]  
• Xia, Z.-B., Anderson, M., Diaz, M. O., Zeleznik-Le, N. J. (2003). MLL repression domain interacts with histone deacetylases, the polycomb group proteins HPC2 and BMI-1, and the corepressor C-terminal-binding protein. Proc. Natl. Acad. Sci. USA 100: 8342-8347 [Abstract] [Full Text]  
• Smith, S. M., Le Beau, M. M., Huo, D., Karrison, T., Sobecks, R. M., Anastasi, J., Vardiman, J. W., Rowley, J. D., Larson, R. A. (2003). Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series. Blood 102: 43-52 [Abstract] [Full Text]  
• Oguchi, K., Takagi, M., Tsuchida, R., Taya, Y., Ito, E., Isoyama, K., Ishii, E., Zannini, L., Delia, D., Mizutani, S. (2003). Missense mutation and defective function of ATM in a childhood acute leukemia patient with MLL gene rearrangement. Blood 101: 3622-3627 [Abstract] [Full Text]  
• Polak, P. E., Simone, F., Kaberlein, J. J., Luo, R. T., Thirman, M. J. (2003). ELL and EAF1 are Cajal Body Components That Are Disrupted in MLL-ELL Leukemia. Mol. Biol. Cell 14: 1517-1528 [Abstract] [Full Text]  
• Simone, F., Luo, R. T., Polak, P. E., Kaberlein, J. J., Thirman, M. J. (2003). ELL-associated factor 2 (EAF2), a functional homolog of EAF1 with alternative ELL binding properties. Blood 101: 2355-2362 [Abstract] [Full Text]  
• Hsieh, J. J.-D., Ernst, P., Erdjument-Bromage, H., Tempst, P., Korsmeyer, S. J. (2003). Proteolytic Cleavage of MLL Generates a Complex of N- and C-Terminal Fragments That Confers Protein Stability and Subnuclear Localization. Mol. Cell. Biol. 23: 186-194 [Abstract] [Full Text]  
• Dohner, K., Tobis, K., Ulrich, R., Frohling, S., Benner, A., Schlenk, R. F., Dohner, H. (2002). Prognostic Significance of Partial Tandem Duplications of the MLL Gene in Adult Patients 16 to 60 Years Old With Acute Myeloid Leukemia and Normal Cytogenetics: A Study of the Acute Myeloid Leukemia Study Group Ulm. JCO 20: 3254-3261 [Abstract] [Full Text]  
• Ono, R., Taki, T., Taketani, T., Taniwaki, M., Kobayashi, H., Hayashi, Y. (2002). LCX, Leukemia-associated Protein with a CXXC Domain, Is Fused to MLL in Acute Myeloid Leukemia with Trilineage Dysplasia Having t(10;11)(q22;q23). Cancer Res. 62: 4075-4080 [Abstract] [Full Text]  
• Remstein, E. D., Kurtin, P. J., James, C. D., Wang, X.-Y., Meyer, R. G., Dewald, G. W. (2002). Mucosa-Associated Lymphoid Tissue Lymphomas with t(11;18)(q21;q21) and Mucosa-Associated Lymphoid Tissue Lymphomas with Aneuploidy Develop Along Different Pathogenetic Pathways. Am. J. Pathol. 161: 63-71 [Abstract] [Full Text]  
• Sandlund, J. T., Harrison, P. L., Rivera, G., Behm, F. G., Head, D., Boyett, J., Rubnitz, J. E., Gajjar, A., Raimondi, S., Ribeiro, R., Hudson, M., Relling, M., Evans, W., Pui, C.-H. (2002). Persistence of lymphoblasts in bone marrow on day 15 and days 22 to 25 of remission induction predicts a dismal treatment outcome in children with acute lymphoblastic leukemia. Blood 100: 43-47 [Abstract] [Full Text]  
• Shields, J. M., Mehta, H., Pruitt, K., Der, C. J. (2002). Opposing Roles of the Extracellular Signal-Regulated Kinase and p38 Mitogen-Activated Protein Kinase Cascades in Ras-Mediated Downregulation of Tropomyosin. Mol. Cell. Biol. 22: 2304-2317 [Abstract] [Full Text]  
• Park, K. U., Lee, D. S., Lee, H. S., Kim, C. J., Cho, H. I. (2001). Granulocytic Sarcoma in MLL-Positive Infant Acute Myelogenous Leukemia : Fluorescence in Situ Hybridization Study of Childhood Acute Myelogenous Leukemia for Detecting MLL Rearrangement. Am. J. Pathol. 159: 2011-2016 [Abstract] [Full Text]  
• Stanulla, M., Chhalliyil, P., Wang, J., Jani-Sait, S. N., Aplan, P. D. (2001). Mechanisms of MLL gene rearrangement: site-specific DNA cleavage within the breakpoint cluster region is independent of chromosomal context. Hum Mol Genet 10: 2481-2491 [Abstract] [Full Text]  
• Luo, R. T., Lavau, C., Du, C., Simone, F., Polak, P. E., Kawamata, S., Thirman, M. J. (2001). The Elongation Domain of ELL Is Dispensable but Its ELL-Associated Factor 1 Interaction Domain Is Essential for MLL-ELL-Induced Leukemogenesis. Mol. Cell. Biol. 21: 5678-5687 [Abstract] [Full Text]  
• Simone, F., Polak, P. E., Kaberlein, J. J., Luo, R. T., Levitan, D. A., Thirman, M. J. (2001). EAF1, a novel ELL-associated factor that is delocalized by expression of the MLL-ELL fusion protein. Blood 98: 201-209 [Abstract] [Full Text]  
• Fair, K., Anderson, M., Bulanova, E., Mi, H., Tropschug, M., Diaz, M. O. (2001). Protein Interactions of the MLL PHD Fingers Modulate MLL Target Gene Regulation in Human Cells. Mol. Cell. Biol. 21: 3589-3597 [Abstract] [Full Text]  
• Kuwada, N., Kimura, F., Matsumura, T., Yamashita, T., Nakamura, Y., Wakimoto, N., Ikeda, T., Sato, K., Motoyoshi, K. (2001). t(11;14)(q23;q24) Generates an MLL-Human Gephyrin Fusion Gene along with a de facto Truncated MLL in Acute Monoblastic Leukemia. Cancer Res. 61: 2665-2669 [Abstract] [Full Text]  
• Johnson, C. A (2000). Chromatin modification and disease. J. Med. Genet. 37: 905-915 [Full Text]  
• Strissel, P. L., Strick, R., Tomek, R. J., Roe, B. A., Rowley, J. D., Zeleznik-Le, N. J. (2000). DNA structural properties of AF9 are similar to MLL and could act as recombination hot spots resulting in MLL/AF9 translocations and leukemogenesis. Hum Mol Genet 9: 1671-1679 [Abstract] [Full Text]  
• Raimondi, S. C., Chang, M. N., Ravindranath, Y., Behm, F. G., Gresik, M. V., Steuber, C. P., Weinstein, H. J., Carroll, A. J. (1999). Chromosomal Abnormalities in 478 Children With Acute Myeloid Leukemia: Clinical Characteristics and Treatment Outcome in a Cooperative Pediatric Oncology Group Study---POG 8821. Blood 94: 3707-3716 [Abstract] [Full Text]  
• Gordon, L. I., Young, M., Weller, E., Habermann, T. M., Winter, J. N., Glick, J., Ghosh, C., Flynn, P., Cassileth, P. A. (1999). A Phase II Trial of 200% ProMACE-CytaBOM in Patients With Previously Untreated Aggressive Lymphomas: Analysis of Response, Toxicity, and Dose Intensity. Blood 94: 3307-3314 [Abstract] [Full Text]  
• Webb, J. C., Golovleva, I., Simpkins, A. H., Kempski, H., Reeves, B., Sturt, N., Chessells, J. M., Brickell, P. M. (1999). Loss of Heterozygosity and Microsatellite Instability at the MLL Locus Are Common in Childhood Acute Leukemia, but not in Infant Acute Leukemia. Blood 94: 283-290 [Abstract] [Full Text]  
• Heaney, M. L., Golde, D. W. (1999). Myelodysplasia. NEJM 340: 1649-1660 [Full Text]  
• Osaka, M., Rowley, J. D., Zeleznik-Le, N. J. (1999). MSF (MLL septin-like fusion), a fusion partner gene of MLL, in a therapy-related acute myeloid leukemia with a t(11;17)(q23;q25). Proc. Natl. Acad. Sci. USA 96: 6428-6433 [Abstract] [Full Text]  
• Strissel, P. L., Strick, R., Rowley, J. D., Zeleznik-Le, N. J. (1998). An In Vivo Topoisomerase II Cleavage Site and a DNase I Hypersensitive Site Colocalize Near Exon 9 in the MLL Breakpoint Cluster Region. Blood 92: 3793-3803 [Abstract] [Full Text]  
• Schnittger, S., Wormann, B., Hiddemann, W., Griesinger, F. (1998). Partial Tandem Duplications of the MLL Gene Are Detectable in Peripheral Blood and Bone Marrow of Nearly All Healthy Donors. Blood 92: 1728-1734 [Abstract] [Full Text]  
• Taki, T., Shibuya, N., Taniwaki, M., Hanada, R., Morishita, K., Bessho, F., Yanagisawa, M., Hayashi, Y. (1998). ABI-1, a Human Homolog to Mouse Abl-Interactor 1, Fuses the MLL Gene in Acute Myeloid Leukemia With t(10;11)(p11.2;q23). Blood 92: 1125-1130 [Abstract] [Full Text]  
• Hunger, S. P., Cleary, M. L. (1998). What Significance Should We Attribute to the Detection of MLL Fusion Transcripts?. Blood 92: 709-711 [Full Text]  
• Dreyling, M.H., Schrader, K., Fonatsch, C., Schlegelberger, B., Haase, D., Schoch, C., Ludwig, W.-D., Loffler, H., Buchner, T., Wormann, B., Hiddemann, W., Bohlander, S.K. (1998). MLL and CALM Are Fused to AF10 in Morphologically Distinct Subsets of Acute Leukemia With Translocation t(10;11): Both Rearrangements Are Associated With a Poor Prognosis. Blood 91: 4662-4667 [Abstract] [Full Text]  
• Faderl, S., Kantarjian, H. M., Talpaz, M., Estrov, Z. (1998). Clinical Significance of Cytogenetic Abnormalities in Adult Acute Lymphoblastic Leukemia. Blood 91: 3995-4019 [Full Text]  
• Barth, T. F.E., Dohner, H., Werner, C. A., Stilgenbauer, S., Schlotter, M., Pawlita, M., Lichter, P., Moller, P., Bentz, M. (1998). Characteristic Pattern of Chromosomal Gains and Losses in Primary Large B-Cell Lymphomas of the Gastrointestinal Tract. Blood 91: 4321-4330 [Abstract] [Full Text]  
• Gale, K. B., Ford, A. M., Repp, R., Borkhardt, A., Keller, C., Eden, O. B., Greaves, M. F. (1997). Backtracking leukemia to birth: Identification of clonotypic gene fusion sequences in neonatal blood spots. Proc. Natl. Acad. Sci. USA 94: 13950-13954 [Abstract] [Full Text]  
• Mrozek, K., Heinonen, K., Lawrence, D., Carroll, A. J., Koduru, P. R.K., Rao, K. W., Strout, M. P., Hutchison, R. E., Moore, J. O., Mayer, R. J., Schiffer, C. A., Bloomfield, C. D. (1997). Adult Patients With De Novo Acute Myeloid Leukemia and t(9; 11)(p22; q23) Have a Superior Outcome to Patients With Other Translocations Involving Band 11q23: A Cancer and Leukemia Group B Study. Blood 90: 4532-4538 [Abstract] [Full Text]  
• Hess, J. L., Yu, B. D., Li, B., Hanson, R., Korsmeyer, S. J. (1997). Defects in Yolk Sac Hematopoiesis in Mll-Null Embryos. Blood 90: 1799-1806 [Abstract] [Full Text]  
• Sobulo, O. M., Borrow, J., Tomek, R., Reshmi, S., Harden, A., Schlegelberger, B., Housman, D., Doggett, N. A., Rowley, J. D., Zeleznik-Le, N. J. (1997). MLL is fused to CBP, a histone acetyltransferase, in therapy-related acute myeloid leukemia with a t(11;16)(q23;p13.3). Proc. Natl. Acad. Sci. USA 94: 8732-8737 [Abstract] [Full Text]  
• Tenen, D. G., Hromas, R., Licht, J. D., Zhang, D.-E. (1997). Transcription Factors, Normal Myeloid Development, and Leukemia. Blood 90: 489-519 [Full Text]  
• Hilden, J. M., Smith, F. O., Frestedt, J. L., McGlennen, R., Howells, W. B., Sorensen, P. H.B., Arthur, D. C., Woods, W. G., Buckley, J., Bernstein, I. D., Kersey, J. H. (1997). MLL Gene Rearrangement, Cytogenetic 11q23 Abnormalities, and Expression of the NG2 Molecule in Infant Acute Myeloid Leukemia. Blood 89: 3801-3805 [Abstract] [Full Text]  
• Dohner, H., Stilgenbauer, S., James, M. R., Benner, A., Weilguni, T., Bentz, M., Fischer, K., Hunstein, W., Lichter, P. (1997). 11q Deletions Identify a New Subset of B-Cell Chronic Lymphocytic Leukemia Characterized by Extensive Nodal Involvement and Inferior Prognosis. Blood 89: 2516-2522 [Abstract] [Full Text]  
• Thirman, M. J., Diskin, E. B., Bin, S. S., Ip, H. S., Miller, J. M., Simon, M. C. (1997). Developmental analysis and subcellular localization of the murine homologue of ELL. Proc. Natl. Acad. Sci. USA 94: 1408-1413 [Abstract] [Full Text]  
• Pui, C.-H. (1995). Childhood Leukemias. NEJM 332: 1618-1630 [Full Text]  
• Schichman, S. A., Canaani, E., Croce, C. M. (1995). Self-fusion of the ALL 1 Gene: A New Genetic Mechanism for Acute Leukemia. JAMA 273: 571-576 [Abstract]  
• Nucifora, G., Rowley, J.D. (1994). The AML1 Gene in the 8;21 and 3;21 Translocations in Chronic and Acute Myeloid Leukemia. Cold Spring Harb Symp Quant Biol 59: 595-605 [Abstract]  
• Rowley, J. D., Aster, J. C., Sklar, J. (1993). The Clinical Applications of New DNA Diagnostic Technology on the Management of Cancer Patients. JAMA 270: 2331-2337 [Abstract]  
• Cleary, M. L. (1993). A Promiscuous Oncogene in Acute Leukemia. NEJM 329: 958-959 [Full Text]  
• Kourlas, P. J., Strout, M. P., Becknell, B., Veronese, M. L., Croce, C. M., Theil, K. S., Krahe, R., Ruutu, T., Knuutila, S., Bloomfield, C. D., Caligiuri, M. A. (2000). Identification of a gene at 11q23 encoding a guanine nucleotide exchange factor: Evidence for its fusion with MLL in acute myeloid leukemia. Proc. Natl. Acad. Sci. USA 97: 2145-2150 [Abstract] [Full Text]  
• Lavau, C., Luo, R. T., Du, C., Thirman, M. J. (2000). Retrovirus-mediated gene transfer of MLL-ELL transforms primary myeloid progenitors and causes acute myeloid leukemias in mice. Proc. Natl. Acad. Sci. USA 97: 10984-10989 [Abstract] [Full Text]