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Isodicentric (X)(q13): A new characteristic chromosomal anomaly in myeloproliferative syndrome?
Isodicentric (X)(q13): A New Characteristic Chromosomal Anomaly in Myeloproliferative Syndrome? P. Petit, J. P. Fryns, R. Masure, and H. Van Den Berghe
An elderly w o m a n h a d dysmyelopoietic s y n d r o m e with a rapidly fatal course. O n initial marrow and unstimulated blood cell examination a structural anomaly of the X chromosome was observed with a 46,X,idic(X)(q13) karyotype with the exception of two cells showing u 47,XXX karyotype. Peripheral blood lymphocytes showed a normal 46,XX karyotype. The specificity of these findings is discussed.
ABSTRACT:
INTRODUCTION Structural abnormalities of the X chromosome in myeloproliferative disorders are rare findings. Recently, Dewald et al. [1] described an isodicentric X [idicCX)] chromosome with (X)(ql3) break points in bone marrow cells of two patients with preleukemia. The present report deals with an additional case of a structural anomaly of the X chromosome, idic(X)(q13), in an elderly woman with dysmyelopoietic syndrome. CASE REPORT AND CYTOGENETIC FINDINGS T.F., a 80-year-old Belgian femalo, was examined at home because of general weakness. Past medical history was negative, and she has never been exposed to any known toxic agents. Except for pallor and ecchymoses the clinical examination was unremarkable. Hematologic examination revealed marked normocytic anemia (hemoglobin level 7.1 g/dl) with a normal reticulocyte count (1.5%) and a low platelet count (95,000/mm3). There was a slightly increased number of monocytes (19%), but otherwise the peripheral blood was normal and without immature cells. Bone marrow aspiration was normal. Chromosome investigation applying ASG and Rbanding techniques was performed. One hundred bone marrow metaphases were examined. The modal chromosomal number was 46, but an structurally abnormal X chromosome was consistently found with the karyotype 46,X,idic(X)Cq13) (Fig. 1). C-banding techniques revealed an idic(X) chromosome with two blocks of centromeric constitutive heterochromatin (Fig. 2). In 30 unstimulated blood cells the same idic(X) chromosome was observed with the exception of two cells showing a 47,XXX karyotype. Peripheral blood lymphocytes showed a normal 46,XX karyoFrom the Division of Human Genetics, Department of Human Biology, University of Leuven, Leuven, Belgium. A d d r e s s requests for reprints to Dr. H e r m a n Van Den Berghe, Center for H u m a n Genetics, University of Leuven, B-3000 Leuven, Belgium. Received April 24, 1982; accepted M a y 27, 1982.
339 © Elsevier Science Publishing Co., Inc., 1982 52 Vanderbilt Ave., New York, NY 10017
Cancer Genetics and Cytogenetics 7, 339-341 (1982) 0165-4608/82/120339-03502.75
P. Petit et al.
340
Figure 1 The normal X chromosomes in a peripheral blood lymphocyte (left); the triplo-X chromosomes in unstimulated blood cells (middle}; the normal X and idic(X)(q13) [xs] abnormal chromosomes in bone marrow cells (ASG and R-banding). type in 200 cells (Fig. 1). Buccal smears revealed a normally shaped X-chromatin body in 35% of 300 ceils. The patient was never admitted to the hospital. Regular hematological examinations were made during a period of 9 months and showed persistent anemia and thrombocytopenia with a progressive increase in the white blood cell (WBC) count (32.7 × lO°/liter) with 31% monocytes, 14% myelocytes, and 13% metamyelocytes. The bone marrow became hypercellular with a normal myeloid/erythroid ratio and no blast excess. A second chromosome analysis performed 2 months prior to death on bone marrow and unstimulated blood showed the same karyotypic anomaly in all the cells. Except for iron therapy and blood transfusions no other treatment was given and the patient died 10 months after the first hematological checkup.
DISCUSSION The acquired structural anomaly of the X chromosome observed in the present patient is identical to the idic(X)(q13) associated with idiopathic acquired sideroblastic anemia and preleukemia described by Dewald et al. [1]. These authors found a Figure 2 Partial metaphase from bone marrow showing an idic(X} chromosome with two blocks of centromeric constitutive heterochromatin.
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Isodicentric (X)(q13)
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predominant cell line with two idic(X)(q13) chromosomes in two patients and suggested that a selective advantage of these cell line could arise from an ancestral karyotype 46,X,idic(X). In the present patient the abnormal 46,X,idic(X)(q13) karyotype was found in 100% of the marrow and unstimulated blood cells, except for two cells with a 47,XXX karyotype. As no triplo-X cells could be found in peripheral blood lymphocytes, we put forward the hypothesis that originally the proliferating malignant cells had a 47,XXX karyotype and that the 46,X,idic(X) was derived from it after breakage and reunion at q13. The clinical and hematological picture of our patient was initially characterized by anemia, thrombocytopenia, and a slightly increased number of monocytes. Later hyperleukocytosis evolved with 27% immature cells and 31% monocytes and, although no additional investigations including cytochemistry could be performed, we may assume that the patient had dysmyelopoietic or preleukemic syndrome with increased monocytosis and terminal acute myeloblastic leukemia compatible with the French-Amarican-British classification M4. To our knowledge no structural abnormality of the X chromosome has been reported as the sole anomaly in other patients with a hematological malignancy [2,3]. The present case and those reported by Dewald et al. [1] seem to indicate that a 46,X,idic(X) karyotype may characterize certain malignant proliferations and that in those cases the break point is in (X)(q13).
REFERENCES
1. Dewald GW, Pierre RV, Phyliky RL (19811: Three patients with structurally abnormal X chromosomes, each with (X)(q13) break points and a history of idiopathic acquired sideroblastic anemia. Blood 59, 1,100-105. 2. Streuli RA, Testa JR, Vardiman JW, Mintz JW, Colomb HM, Rowley JD (1980): Dysmyelopoietic syndrome: Sequential clinical and cytogenetic studies. Blood 55, 4,636-644. 3. Sandberg AA (1980): The chromosomes in human cancer and leukemia. Elsevier North Holland, New York, pp 257-258.
An elderly w o m a n h a d dysmyelopoietic s y n d r o m e with a rapidly fatal course. O n initial marrow and unstimulated blood cell examination a structural anomaly of the X chromosome was observed with a 46,X,idic(X)(q13) karyotype with the exception of two cells showing u 47,XXX karyotype. Peripheral blood lymphocytes showed a normal 46,XX karyotype. The specificity of these findings is discussed.
ABSTRACT:
INTRODUCTION Structural abnormalities of the X chromosome in myeloproliferative disorders are rare findings. Recently, Dewald et al. [1] described an isodicentric X [idicCX)] chromosome with (X)(ql3) break points in bone marrow cells of two patients with preleukemia. The present report deals with an additional case of a structural anomaly of the X chromosome, idic(X)(q13), in an elderly woman with dysmyelopoietic syndrome. CASE REPORT AND CYTOGENETIC FINDINGS T.F., a 80-year-old Belgian femalo, was examined at home because of general weakness. Past medical history was negative, and she has never been exposed to any known toxic agents. Except for pallor and ecchymoses the clinical examination was unremarkable. Hematologic examination revealed marked normocytic anemia (hemoglobin level 7.1 g/dl) with a normal reticulocyte count (1.5%) and a low platelet count (95,000/mm3). There was a slightly increased number of monocytes (19%), but otherwise the peripheral blood was normal and without immature cells. Bone marrow aspiration was normal. Chromosome investigation applying ASG and Rbanding techniques was performed. One hundred bone marrow metaphases were examined. The modal chromosomal number was 46, but an structurally abnormal X chromosome was consistently found with the karyotype 46,X,idic(X)Cq13) (Fig. 1). C-banding techniques revealed an idic(X) chromosome with two blocks of centromeric constitutive heterochromatin (Fig. 2). In 30 unstimulated blood cells the same idic(X) chromosome was observed with the exception of two cells showing a 47,XXX karyotype. Peripheral blood lymphocytes showed a normal 46,XX karyoFrom the Division of Human Genetics, Department of Human Biology, University of Leuven, Leuven, Belgium. A d d r e s s requests for reprints to Dr. H e r m a n Van Den Berghe, Center for H u m a n Genetics, University of Leuven, B-3000 Leuven, Belgium. Received April 24, 1982; accepted M a y 27, 1982.
339 © Elsevier Science Publishing Co., Inc., 1982 52 Vanderbilt Ave., New York, NY 10017
Cancer Genetics and Cytogenetics 7, 339-341 (1982) 0165-4608/82/120339-03502.75
P. Petit et al.
340
Figure 1 The normal X chromosomes in a peripheral blood lymphocyte (left); the triplo-X chromosomes in unstimulated blood cells (middle}; the normal X and idic(X)(q13) [xs] abnormal chromosomes in bone marrow cells (ASG and R-banding). type in 200 cells (Fig. 1). Buccal smears revealed a normally shaped X-chromatin body in 35% of 300 ceils. The patient was never admitted to the hospital. Regular hematological examinations were made during a period of 9 months and showed persistent anemia and thrombocytopenia with a progressive increase in the white blood cell (WBC) count (32.7 × lO°/liter) with 31% monocytes, 14% myelocytes, and 13% metamyelocytes. The bone marrow became hypercellular with a normal myeloid/erythroid ratio and no blast excess. A second chromosome analysis performed 2 months prior to death on bone marrow and unstimulated blood showed the same karyotypic anomaly in all the cells. Except for iron therapy and blood transfusions no other treatment was given and the patient died 10 months after the first hematological checkup.
DISCUSSION The acquired structural anomaly of the X chromosome observed in the present patient is identical to the idic(X)(q13) associated with idiopathic acquired sideroblastic anemia and preleukemia described by Dewald et al. [1]. These authors found a Figure 2 Partial metaphase from bone marrow showing an idic(X} chromosome with two blocks of centromeric constitutive heterochromatin.
...
,~
: ~::~:i~!~:~
Isodicentric (X)(q13)
341
predominant cell line with two idic(X)(q13) chromosomes in two patients and suggested that a selective advantage of these cell line could arise from an ancestral karyotype 46,X,idic(X). In the present patient the abnormal 46,X,idic(X)(q13) karyotype was found in 100% of the marrow and unstimulated blood cells, except for two cells with a 47,XXX karyotype. As no triplo-X cells could be found in peripheral blood lymphocytes, we put forward the hypothesis that originally the proliferating malignant cells had a 47,XXX karyotype and that the 46,X,idic(X) was derived from it after breakage and reunion at q13. The clinical and hematological picture of our patient was initially characterized by anemia, thrombocytopenia, and a slightly increased number of monocytes. Later hyperleukocytosis evolved with 27% immature cells and 31% monocytes and, although no additional investigations including cytochemistry could be performed, we may assume that the patient had dysmyelopoietic or preleukemic syndrome with increased monocytosis and terminal acute myeloblastic leukemia compatible with the French-Amarican-British classification M4. To our knowledge no structural abnormality of the X chromosome has been reported as the sole anomaly in other patients with a hematological malignancy [2,3]. The present case and those reported by Dewald et al. [1] seem to indicate that a 46,X,idic(X) karyotype may characterize certain malignant proliferations and that in those cases the break point is in (X)(q13).
REFERENCES
1. Dewald GW, Pierre RV, Phyliky RL (19811: Three patients with structurally abnormal X chromosomes, each with (X)(q13) break points and a history of idiopathic acquired sideroblastic anemia. Blood 59, 1,100-105. 2. Streuli RA, Testa JR, Vardiman JW, Mintz JW, Colomb HM, Rowley JD (1980): Dysmyelopoietic syndrome: Sequential clinical and cytogenetic studies. Blood 55, 4,636-644. 3. Sandberg AA (1980): The chromosomes in human cancer and leukemia. Elsevier North Holland, New York, pp 257-258.