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Translocation t(6;9)(p23;q34) in acute nonlymphocytic leukemia
Translocation t(6;9)(p2 Nonly ic Leuk Two New Patients Without Increased Bone Marrow Basophils A t(6:9) has been reported in 30 patients with different malignant myeloproliferative disorders (l-16). Increased numbers of marrow basophils were noted by Pearson et 4. (8) in eight of nine patients with acute nonlymphocytic leukemia (ANAL). However, this feature has not been emphasized by other authors. Recently, Heim et al. (14) and Fonatsch et al. (15) indicated that the number of marrow basophils was normal in an ANLL-M4 complicating a myelodysplastic syndrome, in a case of ANLL-M2, and in a caqe with smoldering leukemia. We here report two new ANLL
cases associated with ti6:9) but without an increase of marrow basophils. Patient 1 was a !%-year-old white female who presented with a %&month history of general weakness, dyspnea, and ankle edema starting in December 1985. A complete blood count revealed a hemoglobin of 10.8 g/dl, a white blood cell count (WBC) of 10.6 x lO!‘/L, and a platelet count of 45 x lO”/L. Bone marrow aspiration performed on December 20, 1985, revealed a hypercellular specimen with 39.6% myeloblasts, 32.4% promyelocytes. 7.6% normal lymphoid cells. and 0.2% normal erythroid precursors. A diagnosis of ANLL-M2 was established. Chemotherapy was initiated on December 26, 1985, with cytosine arabinoside and adriarnycin. After having entered complete remission, the patient received consolidation therapy for four courses. The patient relapsed with leukemia in November 1986 and expired on November 16, 1986, due to hemorrhage during attempted placement of a Hickman catheter. Patient 2 is a &year-old white female who had flu-like symptoms and anemia when she was admitted on February 13, 1987. Blood study showed a hemoglobin of 9.2 g/d], a platelet count of 11.7 x lO!‘/L, a WBC of 11.3 X lO!‘/L with 34% neutrophils, 8% bands, 9% motamyelocytes, 24% myelocytes, 3% blasts, 14% lymphocytes, and 6% monocytes. The bone marrow was 90% to 100% cellular, replaced
mostly by immature cells with some variation in cellular maturation, ranging from blasts to cells with more abundant cytoplasm and nuclear irregularity, suggesting myelomonocytic differentiation. The peroxidase stain was positive and ANLL-M4 was diagnosed. After two rounds of chemotherapy consisting of daunomycin, cytosine arabinoside, and 6-thioguanine, the patient entered complete remission and was discharged on April 8, 1987, in good condition. cells with a Cytogenetic studies of bone marrow revealed exclusively t(6;9)(p23;q34) in these two patients (Fig. I), although both of them had a normal karyotype of 46,xX in all phytohemagglutinin-stimulated lymphocytes. Patient 1 developed a karyotype of 47,XX,t(6;9)(p23;q34), + 8 in the bone marrow cells 1 year later. Neither an increased number of marrow basophils nor Auer rods were found in these two patients. Thus, at least six patients with t(6:9) including three cases of M4 (8,14), two cases of M2 (15). and one case of smoldering leukemia (15) without an increased number of marrow basophils have been described. An increase of bone
153 0 1988 Elsevier Science Publishing Co., Inc. 52 Vanderbilt Ave., New York, NY 10017
Cancer Genet Cytogenet 32:153-155 (1986) 0165-4608/88/$03.50
154
Y. Fan et al.
A
O
f
B
6
9
Figure I Two partial karyotypes from patient I (A) and patient 2 (B) showing the translocation t(6;9}{p23:q34}. Arrows indicate the breakpoints ill chromosomes 6 and 9, respectively.
marrow basophils therefore does not seem to be an indispensible feature of ANLL associated with t(6;9). YAO-SHAN FAN Departments of Genetics and Endocrinology and Hematologic Oncology, SHEILA N. JANi SAlT Roswell Park Memorial Institute, Buffalo, NY AZRA RAZA JACOB M. ROWE PETER D'ARRIGO AVERY A. SANDBERG
Strong Memorial Hospital, The University of Rochester, Rochester. NY Millard Fillmore Hospital, Buffalo, NY The Cancer Center Southwest Biomedical Research Institute Scottsdale, AZ
REFERENCES 1. Testa JR, Mintz U. Rowley JD, Vardiman JW, Golomb HM {1979}: Evolution of karyotypes ill acute nonlymphocytic leukemia. Cancer Res 39:3619-3627. 2. Schwartz S, Jiji R. Kerman S. Meekins J. Cohen MM {1983}: Translocation t{6:9}(p23:q34}
t(6;9)(p23;q34) in ANLL
155
in acute nonlymphocytic leukemia. Cancer Genet Cytogenet 10:133-138. 3. Carroll AJ. Castleberrv RP. Prchal JT, Finley WH {1985): Translocation {6:9)(p23:q34} in acute nonlymphocytic leukvmia: Three new cases. Cancer Genet Cytogenet 18:303-306. 4. Fleischman EW. Prigogina EL, Jijinskaja GW. Konstantingva LN. Puchkova GP. Vo!kgva MA, Frenkel MA. Balakirev SA {1983}: Chromosomal rearrangements with a common breakpoint at 6p23 in five case~ of myeloid leukemia. Hum Genet 64:254-256. 5. Sandberg AA, Morgan R, McCailister iA. Kaiser-McCaw B, Hecht F {1983): Acute myeloblastic leukemia {AML) with t(6:9){p23:q34): A specific subgroup of AML? Cancer Genet Cytogenet 10:139--142. 6. Ver~aelen K, Michaux IL. Louwagie A, Van den Berghe H {1983}: Reciprocal translocation t{6:9}{p21.q33}: A new characteristic chromosome anomaly in myeloid leukemias. Cancer Genet Cytogenet 10:125-131. 7. Yunis JJ° Brunning RD, Howe RB, Lobell M (1984): High resolution chromosomes as an independent prognostic indicator in adult acute nonlymphocytic leukemia. N Engl J Med 311:812-818. 8. Pearson MG, Vardiman lW, LeBeau MM. Rowley JD, Schwartz S. Kerman SL, Cohen MM, Fieischman EW. Prigogina EL [!985): Inrreased numbeis of ihJdiio~ ba:~ophtis may 0e associated with ~ ~(~.~) m ANLL. Am J Hematol 18:393-403. 9. Rowley JD, Potter D {1976): Chromosomal banding patterns in acute nonlymphocytic leukemia. Blood 47:705-721. 10. Fitzgerald PH. Morris CM, Fraser GJ. Giles LM, Hamer JW, Heaton DC, Beard ME] {1983): Nonrandom cytogenetic changes in New Zealand patients with acute myeloid leukemia. Cancer Genet Cytogenet 8:51-66. 11. Mitelman F {1985): Catalog of Chromosome Aberrations in Cancer. in: Progress and Topics in Cytogenetics. Vol. 5. A. A. Sandberg Ed.. 2nd Ed. Alan R Liss. New York. 12. Puchkova GP. Prigogina EL. F|eischman EW. Drosdova TS, Mayakova SA. Peterson IS {1983}: Chromosome abnormalities in chronic myeloid leukemia in children. Hum Genet 64:257-262.
13. Gold El. Conjalka M, Pelus LM, Ihanwar SC. Broxmeyer H. Middleton AB, Clarkson BD, Moore MAS (1983): Marrow cytogenetic and cell culture analyses of the myelodysplastic syndromes: Insights to pathopllysiology and prognosis. J Clin Oncol 1:627-634. 114. Heim S, Kristoffersson U, Mandahl N, Mitehnan F. Bekassy AN, Garwicz S, Wiebe T (19~6}: High resolution banding analysis of the reciprocal translocation t{6;9) in acute nonlym phocytic leukemia. Cancer Genet Cytogenet 22:195-201. 15. Fonatsch C, Stolhnann B, Holhlack J. Engert A (1987): Translocation (6;9)(p23;q34} in smoldering leukemia and acute nonlymphocytic leukemia. Cancer Genet Cytogenet 26:363-368. 16. Fan YS, Raza A, Jani-Sait SN, Block A, Schumer J, Snyderman M, Sandberg AA (1987): Translocation t(6:c3}(p22.3;q34} i~.w,myelodysplastic syndrome-refractory anemia with excess blasts. Cancer Genet Cytogenet 29:135-138.
cases associated with ti6:9) but without an increase of marrow basophils. Patient 1 was a !%-year-old white female who presented with a %&month history of general weakness, dyspnea, and ankle edema starting in December 1985. A complete blood count revealed a hemoglobin of 10.8 g/dl, a white blood cell count (WBC) of 10.6 x lO!‘/L, and a platelet count of 45 x lO”/L. Bone marrow aspiration performed on December 20, 1985, revealed a hypercellular specimen with 39.6% myeloblasts, 32.4% promyelocytes. 7.6% normal lymphoid cells. and 0.2% normal erythroid precursors. A diagnosis of ANLL-M2 was established. Chemotherapy was initiated on December 26, 1985, with cytosine arabinoside and adriarnycin. After having entered complete remission, the patient received consolidation therapy for four courses. The patient relapsed with leukemia in November 1986 and expired on November 16, 1986, due to hemorrhage during attempted placement of a Hickman catheter. Patient 2 is a &year-old white female who had flu-like symptoms and anemia when she was admitted on February 13, 1987. Blood study showed a hemoglobin of 9.2 g/d], a platelet count of 11.7 x lO!‘/L, a WBC of 11.3 X lO!‘/L with 34% neutrophils, 8% bands, 9% motamyelocytes, 24% myelocytes, 3% blasts, 14% lymphocytes, and 6% monocytes. The bone marrow was 90% to 100% cellular, replaced
mostly by immature cells with some variation in cellular maturation, ranging from blasts to cells with more abundant cytoplasm and nuclear irregularity, suggesting myelomonocytic differentiation. The peroxidase stain was positive and ANLL-M4 was diagnosed. After two rounds of chemotherapy consisting of daunomycin, cytosine arabinoside, and 6-thioguanine, the patient entered complete remission and was discharged on April 8, 1987, in good condition. cells with a Cytogenetic studies of bone marrow revealed exclusively t(6;9)(p23;q34) in these two patients (Fig. I), although both of them had a normal karyotype of 46,xX in all phytohemagglutinin-stimulated lymphocytes. Patient 1 developed a karyotype of 47,XX,t(6;9)(p23;q34), + 8 in the bone marrow cells 1 year later. Neither an increased number of marrow basophils nor Auer rods were found in these two patients. Thus, at least six patients with t(6:9) including three cases of M4 (8,14), two cases of M2 (15). and one case of smoldering leukemia (15) without an increased number of marrow basophils have been described. An increase of bone
153 0 1988 Elsevier Science Publishing Co., Inc. 52 Vanderbilt Ave., New York, NY 10017
Cancer Genet Cytogenet 32:153-155 (1986) 0165-4608/88/$03.50
154
Y. Fan et al.
A
O
f
B
6
9
Figure I Two partial karyotypes from patient I (A) and patient 2 (B) showing the translocation t(6;9}{p23:q34}. Arrows indicate the breakpoints ill chromosomes 6 and 9, respectively.
marrow basophils therefore does not seem to be an indispensible feature of ANLL associated with t(6;9). YAO-SHAN FAN Departments of Genetics and Endocrinology and Hematologic Oncology, SHEILA N. JANi SAlT Roswell Park Memorial Institute, Buffalo, NY AZRA RAZA JACOB M. ROWE PETER D'ARRIGO AVERY A. SANDBERG
Strong Memorial Hospital, The University of Rochester, Rochester. NY Millard Fillmore Hospital, Buffalo, NY The Cancer Center Southwest Biomedical Research Institute Scottsdale, AZ
REFERENCES 1. Testa JR, Mintz U. Rowley JD, Vardiman JW, Golomb HM {1979}: Evolution of karyotypes ill acute nonlymphocytic leukemia. Cancer Res 39:3619-3627. 2. Schwartz S, Jiji R. Kerman S. Meekins J. Cohen MM {1983}: Translocation t{6:9}(p23:q34}
t(6;9)(p23;q34) in ANLL
155
in acute nonlymphocytic leukemia. Cancer Genet Cytogenet 10:133-138. 3. Carroll AJ. Castleberrv RP. Prchal JT, Finley WH {1985): Translocation {6:9)(p23:q34} in acute nonlymphocytic leukvmia: Three new cases. Cancer Genet Cytogenet 18:303-306. 4. Fleischman EW. Prigogina EL, Jijinskaja GW. Konstantingva LN. Puchkova GP. Vo!kgva MA, Frenkel MA. Balakirev SA {1983}: Chromosomal rearrangements with a common breakpoint at 6p23 in five case~ of myeloid leukemia. Hum Genet 64:254-256. 5. Sandberg AA, Morgan R, McCailister iA. Kaiser-McCaw B, Hecht F {1983): Acute myeloblastic leukemia {AML) with t(6:9){p23:q34): A specific subgroup of AML? Cancer Genet Cytogenet 10:139--142. 6. Ver~aelen K, Michaux IL. Louwagie A, Van den Berghe H {1983}: Reciprocal translocation t{6:9}{p21.q33}: A new characteristic chromosome anomaly in myeloid leukemias. Cancer Genet Cytogenet 10:125-131. 7. Yunis JJ° Brunning RD, Howe RB, Lobell M (1984): High resolution chromosomes as an independent prognostic indicator in adult acute nonlymphocytic leukemia. N Engl J Med 311:812-818. 8. Pearson MG, Vardiman lW, LeBeau MM. Rowley JD, Schwartz S. Kerman SL, Cohen MM, Fieischman EW. Prigogina EL [!985): Inrreased numbeis of ihJdiio~ ba:~ophtis may 0e associated with ~ ~(~.~) m ANLL. Am J Hematol 18:393-403. 9. Rowley JD, Potter D {1976): Chromosomal banding patterns in acute nonlymphocytic leukemia. Blood 47:705-721. 10. Fitzgerald PH. Morris CM, Fraser GJ. Giles LM, Hamer JW, Heaton DC, Beard ME] {1983): Nonrandom cytogenetic changes in New Zealand patients with acute myeloid leukemia. Cancer Genet Cytogenet 8:51-66. 11. Mitelman F {1985): Catalog of Chromosome Aberrations in Cancer. in: Progress and Topics in Cytogenetics. Vol. 5. A. A. Sandberg Ed.. 2nd Ed. Alan R Liss. New York. 12. Puchkova GP. Prigogina EL. F|eischman EW. Drosdova TS, Mayakova SA. Peterson IS {1983}: Chromosome abnormalities in chronic myeloid leukemia in children. Hum Genet 64:257-262.
13. Gold El. Conjalka M, Pelus LM, Ihanwar SC. Broxmeyer H. Middleton AB, Clarkson BD, Moore MAS (1983): Marrow cytogenetic and cell culture analyses of the myelodysplastic syndromes: Insights to pathopllysiology and prognosis. J Clin Oncol 1:627-634. 114. Heim S, Kristoffersson U, Mandahl N, Mitehnan F. Bekassy AN, Garwicz S, Wiebe T (19~6}: High resolution banding analysis of the reciprocal translocation t{6;9) in acute nonlym phocytic leukemia. Cancer Genet Cytogenet 22:195-201. 15. Fonatsch C, Stolhnann B, Holhlack J. Engert A (1987): Translocation (6;9)(p23;q34} in smoldering leukemia and acute nonlymphocytic leukemia. Cancer Genet Cytogenet 26:363-368. 16. Fan YS, Raza A, Jani-Sait SN, Block A, Schumer J, Snyderman M, Sandberg AA (1987): Translocation t(6:c3}(p22.3;q34} i~.w,myelodysplastic syndrome-refractory anemia with excess blasts. Cancer Genet Cytogenet 29:135-138.