We report two cases of acute myeloid leukemia (M1 and M5B subtypes) with a similar translocation, t(3;11)(q21;q13). We discuss the involvement of these breakpoints in acute leukemia and their putative clinical implications

Bengoechea, E. (Enrique)

Calasanz-Abinzano, M.J. (Maria Jose)

Cigudosa, J.C. (Juan Cruz)

Gullon, A. (Arturo)

Marin, J. (Julián)

Odero, M.D. (Maria Dolores)

Dadun, University of Navarra

ELSEVIER A Recurrent Translocation, t(3;11)(q21;q13), Found in Two Distinct Cases of Acute Mye|oid Leukemia Juan C. Cigudosa, M. Jos6 Calasanz, M. Dolores Odero, Juli rt Marin, Enrique Bengoechea, and Arturo Gull6n ABSTRACT:  We report wo cases of acute myeloid leukemia (M1 and M5B subtypes) with a similar trans- location, t(3;11)(q21;q13). We discuss the involvement of these breakpoints in acute leukemia and their putative clinical implications. INTRODUCrION Karyotypes with single chromosomal rearrangements involv- ing band q13 of chromosome 11 are a quite rare finding in acute myeloid leukemia (AML) and are associated with cases of M4 and M5 FAB subtypes [1, 2]. Rearrangements of the long arm of chromosome 3 affecting bands q21-q26 have been reported both in cases associated with an abnormal throm- bopoiesis [3-5] and in cases lacking such an association [6, 7]. The joining of both events, that is, rearrangements involv- ing breakpoints 3q26 and 11q13, has been recently described in a case of M4 AML [2]. We report two cases of AML with a reciprocal translocation between chromosomes 3 and 11 with breakpoints at bands q21 and q13, respectively. PATIENTS AND METHODS Pat ient 1 A 58-year-old woman was admitted to the hospital in Au- gust 1993 because of asthenia nd anorexia during the last month. Physical examination revealed pallor and gingival hypertrophy. Blood findings were 17.8 × 109/L white blood cell (WBC) count (56% of atypical monocytes and 2% blasts), hemoglobin 10.1 g/dL, and platelet count 67 x 109/L. After morphologic examination of bone marrow aspirate, a diag- nosis of acute nonlymphocytic leukemia of the FAB subtype M5 B was made. Immunologic markers were as follows: CD45 (100%), CD14 (40%), HLA-DR (90%), CD13 (67%), CD33 (91%), CD56 (53%), and CD16 (16%). A complete remission From the Department of Genetics (M. J. C., M. D. 0., A. G.), University of Navarra, Pamplona; Service of Hematology (J. M., E. B.), Hospital N. Sra de Amnzazu, San Sebastidn; and Service of Cytogenetics (J. C. C.), Faculty of Medicine, University of La Laguna, Canary Islands, Spain. Address reprint requests to: Dr. J. C. Cigudosa, Servicio de Citogen~tica, Facultad de Medicina, Universidad e La Laguna, 38071 La Laguna, Tenerife, Spain. Received August 25, •994; accepted January 24, 1995. was induced after 3 x 7 cycles of treatment with daunoblastin and cytarabine, and the patient now remains asymptomatic. Pat ient 2 A 22-year-old man was admitted to the hospital in Novem- ber 1993 because of pallor. Blood cell counts were 3.4 x 109/L WBC count  (40O/o of blasts), hemoglobin 7.4 g/dL, and platelet count 58 x 109/L. After morphologic examination of bone marrow aspirate, a diagnosis of acute nonlympho- cytic leukemia of the FAB subtype M1 was made. Peroxidase was positive for 38% of blasts, PAS and naftol-acetate-esterase tests were concordant with this diagnosis. A complete remis- sion was induced after 3 x 7 cycles of treatment with doxy- rubicine and cytarabine, and the patient now remains asymp- tomatic. Bone marrow cells were short-term cultured (24-48 hours) and analyzed by standard cytogenetic methods which include Trypsin-Giemsa banding. Samples from both patients were examined at diagnosis, during treatment, and at hematologic remission. RESULTS Patient 1 at diagnosis showed the following karyotype: 46,XX,t(3;11)(q21;q13) in all 30 observed metaphases. Dur- ing the treatment we performed a new analysis and we ob- served 20 metaphases with normal karyotype and 15 meta- phases with the same t(3;11) translocation. Once hematologic remission was achieved, anew sample was analyzed and we saw only normal cells, confirming the remission also at the cytogenetic level. Patient 2 had a similar cytogenetic story. At diagnosis, 10 cells showed a normal karyotype and 15 cells showed the following karyotype: 46,XY, t(3;11)(q21;q13). During the treat- ment the proportion of normal cells increased (20 normal cells, 10 cells with the translocation), and finally, when hematologic remission was induced only normal cells were seen. Partial karyotypes of both cases are shown in Figure 1. Cancer Genet Cytogenet 83:119-120 (1995) © Elsevier Science Inc., 1995 655 Avenue of the Americas, New York, NY 10010 0165-4608/95/$9.50 SSDI 0165-4608(95)00019-L 120 J.C. Cigudosa et al. A .,q B 3 11 Figure 1 Partial karyotype of patients I (A) and 2 (B) with a simi- lar t(3;11)(q21;q13) translocation. Arrowheads how the involved breakpoints. DISCUSSION From the cytogenetic point of view, two aspects are of in- terest in this report. Firstly the fact that in both cases, de- spite the presence of rearrangements of band 3q21, abnor- mal megakaryopoiesis was not demonstrable. Thus, the proposed association between breakpoints at 3q21 and 3q26 and that feature [3-5] might be restricted either to the distal breakpoint or to the simultaneous involvements ofboth chro- mosomal segments. We agree with the suggestion of Kwong et al. (1993) about this relationship: rearrangements of 3q26 (3q21 in our case) may play an important role in leukemo- genesis and may or may not affect different candidate genes, with one (some) associated with abnormal thrombopoiesis. On the other hand, the involvement of band 11q13 is not a common finding in AML, however, its recurrence in M4 and M5 FAB subtypes hould be considered for the future. The molecular references for this segment tell us nothing about the role in leukemogenesis in the two genes so far mapped within it [8, 9]. These genes (named BCL-1 and PRAD1) are clearly involved in lymphomagenesis but nothing is known about their importance in AML. Our patients were classified as having M5 B (Patient 1) and M1 (Patient 2) AML. Thus the translocation does not seem to be very specific for a determinate subtype of AML. However, taking together all the reported cases with single chromosomal rearrangements of 11q13, including one of our cases, it is relevant that they correspond to either the M4 or the M5 subtype [1, 2]. If there is a new subset of AML as- sociated with this type of rearrangement it is still not clear, but waits yet to be determined. REFERENCES 1. Mitelman F, (1991): Catalog of Chromosome Aberrations in Can- cer. Fourth Edition. Wiley Liss, New York. 2. Kwong YL, Lie AKW, Chart LC (1993}: A novel translocation (3;11)(q26;q13) in a case of acute myelomonocytic leukemia. Can- cer Genet Cytogenet 69:158-160. 3. Bitter MA, Neilly ME, Le Beau MM, Pearson MG, Rowley JD (1985): Rearrangements of chromosome 3 involving bands 3q21 and 3q26 are associated with normal or elevated platelet counts in acute nonlymphocytic leukemia. Blood 66:1362-1370. 4. Helm S and Mitelman F (1987): Cancer Cytogeneties. New York, Alan R. Liss, Inc., pp 81-85. 5. Jotterand Bellomo M, Parlier V, Muhlemamatter D, Grob JP, Beris PH (1992): Three new cases of chromosome 3 rearrangements in bands q21 and q26 with abnormal thrombopoiesis bring fur- ther evidence to the existence ofa 3q21q26 syndrome. Cancer Ge- net Cytogenet 59:138-160. 6. Raimondi SC, Dube ID, Valentine MB, Miro J, Jim Watt H, Lar- son RA, Bitter MA, LeBeau MM, Rowley JD (1989}: Clinico- pathologic manifestations and breakpoints of the t(3;5) in patients with acute nonlymphocytic leukemia. Leukemia 3:42-47. 7. Rubin CM, Larson RA, Anastasi J, Winter JN, Thangavelu M, Vardiman JW, Rowley JD, Le Beau MM (1990): t(3;21)(q26;q22): a recurring chromosomal bnormality in therapy-related my- elodysplastic syndrome and acute myeloid leukemia. Blood 76:2594-2598. 8. Tsujimoto Y, Yunis J, Onorato-Showe L, Erikson J, Nowell PC, Croce CM (1984): Molecular cloning of the chromosomal break- point of B-cell lymphomas and leukemias with the t(11;14) chro- mosome translocation. Science 224:1403-1406. 9. Motokura T, Bloom T, Kim HG, Jupner H, Ruderman JV, Kronen- berg HM, Arnold A (1991): A novel cyclin encoded by a bcl-1 linked candidate oncogene. Nature 350:512-515. 

A recurrent translocation, t(3;11)(q21;q13), found in two distinct cases of acute myeloid leukemia

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