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Constitutional Robertsonian translocations in (9;22)-positive chronic myelogenous leukemia
Cancer Genetics and Cytogenetics 132 (2002) 79–80
Letter to the editor
Constitutional Robertsonian translocations in (9;22)-positive chronic myelogenous leukemia We report two cases of t(9;22)-positive chronic myelogenous leukemia (CML) with constitutional Robertsonian translocations. The first patient was admitted to the hospital on May 12, 1994 with primary complaints of weakness and emaciation for a month and melena for a day. A physical examination revealed marked pallor and splenomegaly. Peripheral blood counts showed Hb 45g/L, WBC 200 109/L with 60% immature cells. The evidence of CML was provided by a bone marrow (BM) aspirate, which showed hypercellularity with 27% neutrophils, 24% metamyelocytes, 20% myelocytes, 10% promyelocytes, and 1.5% blasts. Cytogenetic analysis revealed the following karyotypes: 45,XY,t(9;22)(q34;q11), der(13;14)(q10;q10)[20] (Fig. 1) in BM cells and 45,XY,der(13;14)(q10;q10)[20] in peripheral blood lymphocytes, respectively. The second patient was diagnosed with CML in a local hospital 5 years ago and treated with hydroxyurea. He was transferred to our hospital on July 21, 2000 with symptoms of weakness, fever, and chest pain. Physical examination revealed no obvious abnormality only mild pallor. Peripheral blood counts revealed the following: Hb 98 g/L, WBC 15.4 109/L with a differential of 46% neutrophils, 7% myelocytes, 6% basophils, 5% eosinophils, 3% metamyelocytes, 2% blasts, 2% promyelocytes, and platelets 988 109/L. The BM aspirate was hypercellular with 25.0% bands, 16.5% metamyelo-
Fig. 1. R-banded karyotype from a bone marrow cell of patient 1 showing 45,XY,t(9;22) (q34;q11),der(13;14)(q10;q10).
cytes, 11.5% neutrophils, 8% blasts, 3% myelocytes, and 1% promyelocytes. Neutrophillic alkaline phosphatase of peripheral blood was negative. Mild splenomegaly was found by ultrasonic examination. Cytogenetic analysis showed a 14;22 Robertsonian translocation and a t(9; 22)(q34;q11) in his BM metaphase cells. Interestingly, chromosome 22 involved in the t(9;22) and in the rob(14; 22) was identical. Thus, his karyotype would be described as 45,XY,t(9;22)(q34;q11), der(14;22)(q10;q10) (Fig. 2). Subsequent karyotyping on the patient’s peripheral blood lymphocytes and those of his son and daughter revealed a der(14;22) as a sole abnormality in all analyzed metaphases. M-bcr/abl fusion transcript (b3a2) was detected in his BM cells by Reverse-transcription polymerase chain reaction (RT-PCR). Robertsonian translocations, although relatively common as a constitutional cytogenetic aberration, are rarely encountered in CML. Kohno et al. [1] reported the first case in 1978. Other authors subsequently reported two other cases [2,3]. The present patient 2, had the same t(14;22) as seen in the patient reported by Becher et al. [3]. However, chromosome 22 involved in the t(14;22) and t(9;22) of patient 2 was identical, unlike the patient reported [3]. The RT-PCR also demonstrated that this translocation resulted
Fig. 2. R-banded karyotype from a bone marrow cell of patient 2 showing 44,XY,t(9;22)(q34;q11), der(14;22)(q10;q10),17; chromosome 17 was a random loss; Philadelphia chromosome and derivative chromosome 9 are indicated with an arrow.
0165-4608/02/$ – see front matter © 2002 Elsevier Science Inc. All rights reserved. PII: S0165-4608(01)00 5 2 2 - 2
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J. Qian et al. / Cancer Genetics and Cytogenetics 132 (2002) 79–80
in M-bcr/abl fusion as in most CML patients. As far as we know this translocation pattern was not reported before. On the occurrence of Philadelphia positive CML in a patient with a Robertsonian translocation there are two different opinions: Becher et al. [2,3], thought that a carrier of a Robertsonian translocation had an increased risk for the development of leukemia, while Kohno et al. [1] considered the appearance of the two translocations and the clinical status may be coincidental. We consider that the association between the congenital Robertsonian translocation and Philadelphia positive CML cannot be confirmed or denied at present. It is still a question to be clarified. For this reason, further reports and studies into such cases and their families is necessary. Jun Qian Yongquan Xue Jianzhi Sun Yu Guo
Jinlan Pan Yafang Wu Wei Wang Li Yao Jiangsu Institute of Hematology Leukemia Research Unit First Affiliated Hospital of Suzhou University 296 Shizi Street Suzhou 215006, Peoples Republic of China
References [1] Kohno S, Sandberg AA. Ph1-positive CML in a 13;14 translocation carrier. Med Pediatr Oncol 1978;5:61–4. [2] Becher R, Mahmoud HK, Schaefer UW, Schmidt CG. Ph-positive CML in a family with a constitutional Robertsonian translocation 14; 15. Cancer Genet Cytogenet 1985;18:229–34. [3] Becher R, Wendt F, Kühn D. Constitutional Robertsonian t(15;22) in Ph-positive CML. Hum Genet 1987;76:399.
Letter to the editor
Constitutional Robertsonian translocations in (9;22)-positive chronic myelogenous leukemia We report two cases of t(9;22)-positive chronic myelogenous leukemia (CML) with constitutional Robertsonian translocations. The first patient was admitted to the hospital on May 12, 1994 with primary complaints of weakness and emaciation for a month and melena for a day. A physical examination revealed marked pallor and splenomegaly. Peripheral blood counts showed Hb 45g/L, WBC 200 109/L with 60% immature cells. The evidence of CML was provided by a bone marrow (BM) aspirate, which showed hypercellularity with 27% neutrophils, 24% metamyelocytes, 20% myelocytes, 10% promyelocytes, and 1.5% blasts. Cytogenetic analysis revealed the following karyotypes: 45,XY,t(9;22)(q34;q11), der(13;14)(q10;q10)[20] (Fig. 1) in BM cells and 45,XY,der(13;14)(q10;q10)[20] in peripheral blood lymphocytes, respectively. The second patient was diagnosed with CML in a local hospital 5 years ago and treated with hydroxyurea. He was transferred to our hospital on July 21, 2000 with symptoms of weakness, fever, and chest pain. Physical examination revealed no obvious abnormality only mild pallor. Peripheral blood counts revealed the following: Hb 98 g/L, WBC 15.4 109/L with a differential of 46% neutrophils, 7% myelocytes, 6% basophils, 5% eosinophils, 3% metamyelocytes, 2% blasts, 2% promyelocytes, and platelets 988 109/L. The BM aspirate was hypercellular with 25.0% bands, 16.5% metamyelo-
Fig. 1. R-banded karyotype from a bone marrow cell of patient 1 showing 45,XY,t(9;22) (q34;q11),der(13;14)(q10;q10).
cytes, 11.5% neutrophils, 8% blasts, 3% myelocytes, and 1% promyelocytes. Neutrophillic alkaline phosphatase of peripheral blood was negative. Mild splenomegaly was found by ultrasonic examination. Cytogenetic analysis showed a 14;22 Robertsonian translocation and a t(9; 22)(q34;q11) in his BM metaphase cells. Interestingly, chromosome 22 involved in the t(9;22) and in the rob(14; 22) was identical. Thus, his karyotype would be described as 45,XY,t(9;22)(q34;q11), der(14;22)(q10;q10) (Fig. 2). Subsequent karyotyping on the patient’s peripheral blood lymphocytes and those of his son and daughter revealed a der(14;22) as a sole abnormality in all analyzed metaphases. M-bcr/abl fusion transcript (b3a2) was detected in his BM cells by Reverse-transcription polymerase chain reaction (RT-PCR). Robertsonian translocations, although relatively common as a constitutional cytogenetic aberration, are rarely encountered in CML. Kohno et al. [1] reported the first case in 1978. Other authors subsequently reported two other cases [2,3]. The present patient 2, had the same t(14;22) as seen in the patient reported by Becher et al. [3]. However, chromosome 22 involved in the t(14;22) and t(9;22) of patient 2 was identical, unlike the patient reported [3]. The RT-PCR also demonstrated that this translocation resulted
Fig. 2. R-banded karyotype from a bone marrow cell of patient 2 showing 44,XY,t(9;22)(q34;q11), der(14;22)(q10;q10),17; chromosome 17 was a random loss; Philadelphia chromosome and derivative chromosome 9 are indicated with an arrow.
0165-4608/02/$ – see front matter © 2002 Elsevier Science Inc. All rights reserved. PII: S0165-4608(01)00 5 2 2 - 2
80
J. Qian et al. / Cancer Genetics and Cytogenetics 132 (2002) 79–80
in M-bcr/abl fusion as in most CML patients. As far as we know this translocation pattern was not reported before. On the occurrence of Philadelphia positive CML in a patient with a Robertsonian translocation there are two different opinions: Becher et al. [2,3], thought that a carrier of a Robertsonian translocation had an increased risk for the development of leukemia, while Kohno et al. [1] considered the appearance of the two translocations and the clinical status may be coincidental. We consider that the association between the congenital Robertsonian translocation and Philadelphia positive CML cannot be confirmed or denied at present. It is still a question to be clarified. For this reason, further reports and studies into such cases and their families is necessary. Jun Qian Yongquan Xue Jianzhi Sun Yu Guo
Jinlan Pan Yafang Wu Wei Wang Li Yao Jiangsu Institute of Hematology Leukemia Research Unit First Affiliated Hospital of Suzhou University 296 Shizi Street Suzhou 215006, Peoples Republic of China
References [1] Kohno S, Sandberg AA. Ph1-positive CML in a 13;14 translocation carrier. Med Pediatr Oncol 1978;5:61–4. [2] Becher R, Mahmoud HK, Schaefer UW, Schmidt CG. Ph-positive CML in a family with a constitutional Robertsonian translocation 14; 15. Cancer Genet Cytogenet 1985;18:229–34. [3] Becher R, Wendt F, Kühn D. Constitutional Robertsonian t(15;22) in Ph-positive CML. Hum Genet 1987;76:399.