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Translocation (9;11)(p21;q23) in a case of acute myeloblastic leukemia (AML-M2)
Translocation (9;11)(p21;q23) in a Case of Acute Myeloblastic Leukemia (AML-M2) Andrew J. Carroll, Man-Chiu Poon, N. Carol Robinson, and Wayne H. Finley
ABSTRACT: A patient with acute myeloblastic leukemia (AML-M2) and a balanced translocation, t(9;11)(p21;q23), is described. The translocation appears to be the same as that previously reported in some patients with acute monoblastic leukemia (AMoL-MS). This suggests that, although t(9;11)(p21;q23) frequently may be associated with AMoL, the translocation may not be specific for that disorder. INTRODUCTION The association of specific cytogenetic abnormalities w i t h particular types of acute n o n l y m p h o c y t i c l e u k e m i a (ANLL) is well established [1]. Rearrangements of chrom o s o m e #11 have been reported to be in frequent association w i t h acute monoblastic l e u k e m i a (AMoL-M5) [2, 3]. Other investigators have noted a high frequency of c h r o m o s o m e #11 i n v o l v e m e n t in patients w i t h acute m y e l o m o n o c y t i c l e u k e m i a (AMMoL-M4), as well as those w i t h AMoL [3, 4]. Hagemeijer et al. [4] described three AMoL patients w i t h an identical t(9;11) and suggested that the t(9;11)(p21;q23) might be characteristic for M5 leukemia. Dewald et al. [5] noted a similar translocation, t(9;11)(p22;q24), in 3 of 10 AMoL patients. We have observed this same translocation, t(9;11)(p21;q23), in a patient w i t h acute myeloblastic leukemia (AML-M2), w h i c h suggests that the translocation m a y not be specifically associated w i t h AMoL.
CASE REPORT A 54-year-old white male had a 5-week history of progressive fatigue, malaise, increased bruisability, and prolonged bleeding following m i n o r cuts. He had a periodontal infection and an infection of his left leg requiring antibiotics. T y p e II diabetes mellitus was diagnosed 15 mo prior to presentation a n d was treated with talbutamide (100 rag/day). At presentation, the patient h a d a t e m p e r a t u r e of 38°C, b l o o d pressure 150/80, a n d pulse rate of lO0/min without orthostatic changes. He had a flame-shaped hemorrhage in the fundi and m u l t i p l e petechiae over the lowel extremities. There was no gingival hyperplasia, skin infiltrations, p e r i p h e r a l lymph-
From the Laboratory of Medical Genetics and Division of Hematology and Oncology, University oJ Alabama in Birmingham, and the BirminghamVeterans Administration Medical Center, Birmingham, AL. Address requests for reprints to Dr. Andrew ]. Carroll, Laboratory of Medical Genetics University of Alabama in Birmingham, Birmingham, AL 35294. Received April 1, 1983; accepted August 22, 1983.
3 2 c, © 1984 by Elsevier Science Publishing Co., Inc. 52 Vanderbilt Ave., New York, NY 10017
Cancer Genetics and Cytogenetics 12, 329-33 01654608/84/$03.00
330
A.J. Carroll et al. Table 1
Laboratory data for the patient at the time of presentation
Hemoglobin (g/dl) Hematocrit (ml/dl) WBC (x 109/L) Platelets (× 109/L) MCV (~3) MCHC (%) Differential (%) Blasts Segmented neutrophils Eosinophils Lymphocytes Bone marrow cellularity (%) Bone marrow blasts (%) Auer rods Cytochemical stains (% positive) PAS Sudan black NASD chloroacetate esterase Alpha-napthyl butyrate esterase
4.8 14 1.8 9 111 35 9 5 1 85 90 100 Positive 12 (diffuse) 60 60 <5
adenopathy, or hepatosplenomegaly. The results of laboratory studies are shown in Table 1. The patient received chemotherapy, consisting of daunorubicin 45 mg/m2/ day for 3 days and cytosine arabinoside 100 mg/m2/day for 7 days. After a relatively stormy hospital course, punctuated by sepsis and respiratory failure, he achieved complete remission and was discharged 8 weeks after presentation. Three months later, he suffered a relapse and expired from intracranial hemorrhage complicating thrombocytopenia. CYTOGENETIC STUDIES A bone marrow aspirate, obtained at diagnosis, prior to therapy, was processed directly and following a 24-hr incubation. Routine methods were employed for harvest of the direct preparation. The 24-hr culture was harvested after a 3.5-hr exposure to colcemid (0.06 ~g/ml) at 4°C. Each of the 18 GTG-banded metaphases examined had 46 chromosomes and were initially thought to be normal. Following careful examination, a balanced t(9;11) was noted in every metaphase (Fig. 1). Because the translocation appeared to be the same as that described by Hagemeijer et al. [4], the same breakpoints were assigned, t(9;ll)(p21;q23). DISCUSSION We have observed a patient with AML and t(9;ll)(p21;q23). The diagnosis of AML (M2) in our patient was based on a number of features, including the presence of Auer rods and blasts, which were Sudan black positive, NASD chloroacetate esterase positive, and alpha-napthyl butyrate esterase negative. Although other laboratory data, such as serum and urine lysozyme activity and reactivity to monoclonal antibodies, were not available, we feel that the diagnosis is warranted based on the special stains. After noting the same translocation in 3 of 11 patients with AMoL, but in none of 114 additional ANLL patients, Hagemeijer et al. [4] suggested that the t(9;11) might be specific for AMoL. The presence of t(9;ll) in our patient suggests that this may not be the case.
Figure 1
Karyotype of a bone marrow metaphase showing t(9;ll)(p21;q23). The abnormal chromosomes are identified (arrows).
332
A.J. Carroll et al.
We are aware of four reports in the literature that m e n t i o n patients with ANLI and a t(9;11), similar to that of our patient. Yunis et al. [3] noted a t(9;11)(p22;q24] in a patient with AML (M2). Dewald et al. [5] reported the presence of t(9;11)(p22;q24) in 3 of 10 patients with AMoL and its absence in 143 patients with other types of ANLL. Kaneko et al. [6] reported one AMoL patient with t(9;11)(p22;q23) and m e n t i o n e d a second patient with AMMoL, originally reported by Rowley and Potter [7] as t(?;11)(?;q23), who was found to have t(9;11)(p22;q23] on retrospective analysis. Since the assignment of precise breakpoints for any translocation is subjective to a certain extent, it is entirely possible that our patient and those of Hagemeijer et al., Yunis et al., Dewald et ah, Kaneko et al., and Rowley and Potter have an identical translocation. If this is the case, then only 7 of 1(3 patients with t(9;11)(p21 or 22;q23 or 24) have AMoL. Based on the few reports in the literature, t(9;11)(p21;q23) among patients with ANLL w o u l d appear to be a rather infrequent abnormality; however, its frequency is probably underrated. The difficulty with detecting this translocation has been described [4] and is further illustrated by its retrospective recognition i n our patien! and in others [4, 5, 7]. In conclusion, our data suggest that t(9;11)(p21;q23) may not be limited to cases of AMoL. Further studies are necessary to establish the frequency of this translocation among cases of ANLL and the degree of its association with AMoL and othel conditions. Supported in part by the Bureau of Community Health Services Grant MCJ-905 from DHHS and Veterans Administration Project 7133.
REFERENCES 1. Second International Workshop on Chromosomes in Leukemia, 1979 (1980): General report. Cancer Genet Cytogenet 2:93-96. 2. Berger R, Bernheim A, Web H-J, Daniel M-T, Flandrin G (1980): Cytogenetic studies or acute monocytic leukemia. Leuk Res 4:119-127. 3. Yunis JJ, Bloomfield CD, Ensrud K (1981): All patients with acute nonlymphocytic leukemia may have a chromosomal defect. N Engl J Med 305:135-139. 4. Hagemeijer A, Hahlen K, Sizoo W, Abels J (1982): Translocation (9;11)(p21;q23) in thre~ cases of acute monoblastic leukemia. Cancer Genet Cytogenet 5:95-105. 5. Dewald GW, Morrison-DeLap SJ, Schuchard KA, Spurbeck JL, Pierre RV (1983): A possibl~ specific chromosome marker for monocytic leukemia: Three more patients with t(9;11)(p22;q24) and another with t(11;17)(q24;q21), each with acute monoblastic leukemia. Cancer Genet Cytogenet 8:203-212. 6. Kaneko Y, Rowley JD, Maurer HS, Variokojis D, Moohr JW (1982): Chromosome pattern iN childhood acute nonlymphocytic leukemia (ANLL). Blood 60:389-399. 7. Rowley JD, Potter D (1976): Chromosomal banding patterns in acute nonlymphocytic leukemia. Blood 47:705-721.
ABSTRACT: A patient with acute myeloblastic leukemia (AML-M2) and a balanced translocation, t(9;11)(p21;q23), is described. The translocation appears to be the same as that previously reported in some patients with acute monoblastic leukemia (AMoL-MS). This suggests that, although t(9;11)(p21;q23) frequently may be associated with AMoL, the translocation may not be specific for that disorder. INTRODUCTION The association of specific cytogenetic abnormalities w i t h particular types of acute n o n l y m p h o c y t i c l e u k e m i a (ANLL) is well established [1]. Rearrangements of chrom o s o m e #11 have been reported to be in frequent association w i t h acute monoblastic l e u k e m i a (AMoL-M5) [2, 3]. Other investigators have noted a high frequency of c h r o m o s o m e #11 i n v o l v e m e n t in patients w i t h acute m y e l o m o n o c y t i c l e u k e m i a (AMMoL-M4), as well as those w i t h AMoL [3, 4]. Hagemeijer et al. [4] described three AMoL patients w i t h an identical t(9;11) and suggested that the t(9;11)(p21;q23) might be characteristic for M5 leukemia. Dewald et al. [5] noted a similar translocation, t(9;11)(p22;q24), in 3 of 10 AMoL patients. We have observed this same translocation, t(9;11)(p21;q23), in a patient w i t h acute myeloblastic leukemia (AML-M2), w h i c h suggests that the translocation m a y not be specifically associated w i t h AMoL.
CASE REPORT A 54-year-old white male had a 5-week history of progressive fatigue, malaise, increased bruisability, and prolonged bleeding following m i n o r cuts. He had a periodontal infection and an infection of his left leg requiring antibiotics. T y p e II diabetes mellitus was diagnosed 15 mo prior to presentation a n d was treated with talbutamide (100 rag/day). At presentation, the patient h a d a t e m p e r a t u r e of 38°C, b l o o d pressure 150/80, a n d pulse rate of lO0/min without orthostatic changes. He had a flame-shaped hemorrhage in the fundi and m u l t i p l e petechiae over the lowel extremities. There was no gingival hyperplasia, skin infiltrations, p e r i p h e r a l lymph-
From the Laboratory of Medical Genetics and Division of Hematology and Oncology, University oJ Alabama in Birmingham, and the BirminghamVeterans Administration Medical Center, Birmingham, AL. Address requests for reprints to Dr. Andrew ]. Carroll, Laboratory of Medical Genetics University of Alabama in Birmingham, Birmingham, AL 35294. Received April 1, 1983; accepted August 22, 1983.
3 2 c, © 1984 by Elsevier Science Publishing Co., Inc. 52 Vanderbilt Ave., New York, NY 10017
Cancer Genetics and Cytogenetics 12, 329-33 01654608/84/$03.00
330
A.J. Carroll et al. Table 1
Laboratory data for the patient at the time of presentation
Hemoglobin (g/dl) Hematocrit (ml/dl) WBC (x 109/L) Platelets (× 109/L) MCV (~3) MCHC (%) Differential (%) Blasts Segmented neutrophils Eosinophils Lymphocytes Bone marrow cellularity (%) Bone marrow blasts (%) Auer rods Cytochemical stains (% positive) PAS Sudan black NASD chloroacetate esterase Alpha-napthyl butyrate esterase
4.8 14 1.8 9 111 35 9 5 1 85 90 100 Positive 12 (diffuse) 60 60 <5
adenopathy, or hepatosplenomegaly. The results of laboratory studies are shown in Table 1. The patient received chemotherapy, consisting of daunorubicin 45 mg/m2/ day for 3 days and cytosine arabinoside 100 mg/m2/day for 7 days. After a relatively stormy hospital course, punctuated by sepsis and respiratory failure, he achieved complete remission and was discharged 8 weeks after presentation. Three months later, he suffered a relapse and expired from intracranial hemorrhage complicating thrombocytopenia. CYTOGENETIC STUDIES A bone marrow aspirate, obtained at diagnosis, prior to therapy, was processed directly and following a 24-hr incubation. Routine methods were employed for harvest of the direct preparation. The 24-hr culture was harvested after a 3.5-hr exposure to colcemid (0.06 ~g/ml) at 4°C. Each of the 18 GTG-banded metaphases examined had 46 chromosomes and were initially thought to be normal. Following careful examination, a balanced t(9;11) was noted in every metaphase (Fig. 1). Because the translocation appeared to be the same as that described by Hagemeijer et al. [4], the same breakpoints were assigned, t(9;ll)(p21;q23). DISCUSSION We have observed a patient with AML and t(9;ll)(p21;q23). The diagnosis of AML (M2) in our patient was based on a number of features, including the presence of Auer rods and blasts, which were Sudan black positive, NASD chloroacetate esterase positive, and alpha-napthyl butyrate esterase negative. Although other laboratory data, such as serum and urine lysozyme activity and reactivity to monoclonal antibodies, were not available, we feel that the diagnosis is warranted based on the special stains. After noting the same translocation in 3 of 11 patients with AMoL, but in none of 114 additional ANLL patients, Hagemeijer et al. [4] suggested that the t(9;11) might be specific for AMoL. The presence of t(9;ll) in our patient suggests that this may not be the case.
Figure 1
Karyotype of a bone marrow metaphase showing t(9;ll)(p21;q23). The abnormal chromosomes are identified (arrows).
332
A.J. Carroll et al.
We are aware of four reports in the literature that m e n t i o n patients with ANLI and a t(9;11), similar to that of our patient. Yunis et al. [3] noted a t(9;11)(p22;q24] in a patient with AML (M2). Dewald et al. [5] reported the presence of t(9;11)(p22;q24) in 3 of 10 patients with AMoL and its absence in 143 patients with other types of ANLL. Kaneko et al. [6] reported one AMoL patient with t(9;11)(p22;q23) and m e n t i o n e d a second patient with AMMoL, originally reported by Rowley and Potter [7] as t(?;11)(?;q23), who was found to have t(9;11)(p22;q23] on retrospective analysis. Since the assignment of precise breakpoints for any translocation is subjective to a certain extent, it is entirely possible that our patient and those of Hagemeijer et al., Yunis et al., Dewald et ah, Kaneko et al., and Rowley and Potter have an identical translocation. If this is the case, then only 7 of 1(3 patients with t(9;11)(p21 or 22;q23 or 24) have AMoL. Based on the few reports in the literature, t(9;11)(p21;q23) among patients with ANLL w o u l d appear to be a rather infrequent abnormality; however, its frequency is probably underrated. The difficulty with detecting this translocation has been described [4] and is further illustrated by its retrospective recognition i n our patien! and in others [4, 5, 7]. In conclusion, our data suggest that t(9;11)(p21;q23) may not be limited to cases of AMoL. Further studies are necessary to establish the frequency of this translocation among cases of ANLL and the degree of its association with AMoL and othel conditions. Supported in part by the Bureau of Community Health Services Grant MCJ-905 from DHHS and Veterans Administration Project 7133.
REFERENCES 1. Second International Workshop on Chromosomes in Leukemia, 1979 (1980): General report. Cancer Genet Cytogenet 2:93-96. 2. Berger R, Bernheim A, Web H-J, Daniel M-T, Flandrin G (1980): Cytogenetic studies or acute monocytic leukemia. Leuk Res 4:119-127. 3. Yunis JJ, Bloomfield CD, Ensrud K (1981): All patients with acute nonlymphocytic leukemia may have a chromosomal defect. N Engl J Med 305:135-139. 4. Hagemeijer A, Hahlen K, Sizoo W, Abels J (1982): Translocation (9;11)(p21;q23) in thre~ cases of acute monoblastic leukemia. Cancer Genet Cytogenet 5:95-105. 5. Dewald GW, Morrison-DeLap SJ, Schuchard KA, Spurbeck JL, Pierre RV (1983): A possibl~ specific chromosome marker for monocytic leukemia: Three more patients with t(9;11)(p22;q24) and another with t(11;17)(q24;q21), each with acute monoblastic leukemia. Cancer Genet Cytogenet 8:203-212. 6. Kaneko Y, Rowley JD, Maurer HS, Variokojis D, Moohr JW (1982): Chromosome pattern iN childhood acute nonlymphocytic leukemia (ANLL). Blood 60:389-399. 7. Rowley JD, Potter D (1976): Chromosomal banding patterns in acute nonlymphocytic leukemia. Blood 47:705-721.