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Blastic transformation associated with 5q− and 12p−
Blastic Transformation Associated with
5 q - and 12p-
Abnormalities affecting chromosome 5, mainly long arm deletions, are very common in myelodysplasic syndromes (MDS) but are rarely associated (5%) with chronic myelomonocytic leukemia (CMMoL) [1]. Conversely, deletions of the short arm of chromosome 12 have been reported in 15% of CMMoL in association with secondary leukemia or MDS after treatment with melphalan [2, 3]. We report a case of a 43-yearold man with acute nonlymphocytic leukemia (ANLL) who had generalized weakness, weight loss, edema of the lower limbs, and palpable splenomegaly. On admission the patient's hemoglobin was 7.7 g/dl, total white blood cell count 72 x 109/L with 1% promyelocytes and 40% blast cells, and the platelet count 70 x 109/L. Peripheral blood smears showed the following abnormalities: pseudoPelger cells, macroplatelets, micromegakaryocytes, and micromegakaryoblasts. Cytochemical studies showed that most blasts were positively stained with periodic acidSchiff with a fine granulation, whereas Sudan black B staining was negative, 19% of
Figure 1 Chromosome 5 and 12 in four of the patient's cells, with del(5)(q13q33) and del(12)(p12).
5 ~i¸i~
12
275 © 1990 Elsevier Science Publishing Ca., Inc. 655 A v e n u e of the Americas, New York, NY 10010
Cancer Genet Cytogenet 47:275-276 (]990) 0165-4608/90/$03.50
276
M . L . M, Silva et al. the cells stained faintly with a - n a p h t h y l esterase. The bone marrow aspirate was hypocellular, and the biopsy showed h y p e r c e l l u l a r i t y with immature cells of m y e l o i d origin and n u m e r o u s megakaryocytes with reticular and collagenous fibrosis. This morphological picture suggests not a de novo acute leukemia but an evolution from some type of MDS. Chromosome studies were performed on u n s t i m u l a t e d p e r i p h e r a l blood cells; banding was performed as described by Seabright [4], and the chromosomes were identified and arranged according to the International System for H u m a n Cytogenetic Nomenclature [5]. Forty metaphases were analyzed. In 39 cells, the karyotype was 46,XY,del(5)(q13q33),del(12)(p12) (Fig. 1). In one cell, however, the karyotype was 46,XY,del(12)(p12). These cytogenetic findings reinforce the idea of a secondary leukemia, but because the patient has no previous history of exposure to mutagenic agents, the appearance of the del(12p) is an interesting observation. The 5 q - is a c o m m o n aberration in secondary ANLL as well as in MDS, but according to Bloomfield (1986), in secondary leukemia this a b n o r m a l i t y is more often associated with radiotherapy. However, in the present case, detection of only one cell with a normal c h r o m o s o m e 5 associated with del(12p), although not defining a separate clone, suggests that del(12p) could have occurred before the change in chromosome 5 occurred, w h i c h is probably a secondary event in a previously abnormal cell line. If this is true, del(12p) as the primary event in the present case is i n d e p e n d e n t of c h e m o t h e r a p y followed by a blastic transformation associated with 5q - abnormalities. MARIA LUIZA M. SILVA ALOISIO N. VALENTE DANIEL TABAK JANE DOBBIN JAMISON M. SOUZA ELIANA ABDELHAY MONICA S. O. PEREIRA
Bone Marrow Transplantation National Unit and Hematology Service National Institute of Cancer Rio de Janeiro, Brazil Biophysics Institute Carlos Chagas Filho Federal University of Rio de Janiero Rio de Janeiro, Brazil
REFERENCES
1. Mitelman F, Heim S (1987): Cancer Cytogenetics. Alan R. Liss, New York, p 123. 2. Wilmoth D, Feder M, Finan J, Nowell P (1985): Preleukemia and leukemia with 1 2 p - and 19q + chromosome alterations fallowing alkeran therapy. Cancer Genet Cytogenet 15:95-98. 3. Berger R, Bernheim A, Le Coniat M, Vecchione D, Pacot A, Daniel MT, Flandrin G (1986): Abnormalities of the short arm of chromosome 12 in acute nonlymphocytic leukemia and dysmyelopoietic syndrome. Cancer Genet Cytogenet 19:281-289. 4. Seabright M (1971): A rapid banding technique for human chromosomes. Lancet 2:971-972. 5. ISCN (1978): An International System for Human Cytogenetic Nomenclature. (1978). Birth Defects: Original Article Series, Vol. XIV, No. 8. (The National Foundation, New York, 1978); also in Cytogenet Cell Genet 21:304-404. 6. Bloomfield CD (1986): Chromosome abnormalities in secondary myelodysplastic syndromes. Scand J Haematol 45(Suppl):82-90.
5 q - and 12p-
Abnormalities affecting chromosome 5, mainly long arm deletions, are very common in myelodysplasic syndromes (MDS) but are rarely associated (5%) with chronic myelomonocytic leukemia (CMMoL) [1]. Conversely, deletions of the short arm of chromosome 12 have been reported in 15% of CMMoL in association with secondary leukemia or MDS after treatment with melphalan [2, 3]. We report a case of a 43-yearold man with acute nonlymphocytic leukemia (ANLL) who had generalized weakness, weight loss, edema of the lower limbs, and palpable splenomegaly. On admission the patient's hemoglobin was 7.7 g/dl, total white blood cell count 72 x 109/L with 1% promyelocytes and 40% blast cells, and the platelet count 70 x 109/L. Peripheral blood smears showed the following abnormalities: pseudoPelger cells, macroplatelets, micromegakaryocytes, and micromegakaryoblasts. Cytochemical studies showed that most blasts were positively stained with periodic acidSchiff with a fine granulation, whereas Sudan black B staining was negative, 19% of
Figure 1 Chromosome 5 and 12 in four of the patient's cells, with del(5)(q13q33) and del(12)(p12).
5 ~i¸i~
12
275 © 1990 Elsevier Science Publishing Ca., Inc. 655 A v e n u e of the Americas, New York, NY 10010
Cancer Genet Cytogenet 47:275-276 (]990) 0165-4608/90/$03.50
276
M . L . M, Silva et al. the cells stained faintly with a - n a p h t h y l esterase. The bone marrow aspirate was hypocellular, and the biopsy showed h y p e r c e l l u l a r i t y with immature cells of m y e l o i d origin and n u m e r o u s megakaryocytes with reticular and collagenous fibrosis. This morphological picture suggests not a de novo acute leukemia but an evolution from some type of MDS. Chromosome studies were performed on u n s t i m u l a t e d p e r i p h e r a l blood cells; banding was performed as described by Seabright [4], and the chromosomes were identified and arranged according to the International System for H u m a n Cytogenetic Nomenclature [5]. Forty metaphases were analyzed. In 39 cells, the karyotype was 46,XY,del(5)(q13q33),del(12)(p12) (Fig. 1). In one cell, however, the karyotype was 46,XY,del(12)(p12). These cytogenetic findings reinforce the idea of a secondary leukemia, but because the patient has no previous history of exposure to mutagenic agents, the appearance of the del(12p) is an interesting observation. The 5 q - is a c o m m o n aberration in secondary ANLL as well as in MDS, but according to Bloomfield (1986), in secondary leukemia this a b n o r m a l i t y is more often associated with radiotherapy. However, in the present case, detection of only one cell with a normal c h r o m o s o m e 5 associated with del(12p), although not defining a separate clone, suggests that del(12p) could have occurred before the change in chromosome 5 occurred, w h i c h is probably a secondary event in a previously abnormal cell line. If this is true, del(12p) as the primary event in the present case is i n d e p e n d e n t of c h e m o t h e r a p y followed by a blastic transformation associated with 5q - abnormalities. MARIA LUIZA M. SILVA ALOISIO N. VALENTE DANIEL TABAK JANE DOBBIN JAMISON M. SOUZA ELIANA ABDELHAY MONICA S. O. PEREIRA
Bone Marrow Transplantation National Unit and Hematology Service National Institute of Cancer Rio de Janeiro, Brazil Biophysics Institute Carlos Chagas Filho Federal University of Rio de Janiero Rio de Janeiro, Brazil
REFERENCES
1. Mitelman F, Heim S (1987): Cancer Cytogenetics. Alan R. Liss, New York, p 123. 2. Wilmoth D, Feder M, Finan J, Nowell P (1985): Preleukemia and leukemia with 1 2 p - and 19q + chromosome alterations fallowing alkeran therapy. Cancer Genet Cytogenet 15:95-98. 3. Berger R, Bernheim A, Le Coniat M, Vecchione D, Pacot A, Daniel MT, Flandrin G (1986): Abnormalities of the short arm of chromosome 12 in acute nonlymphocytic leukemia and dysmyelopoietic syndrome. Cancer Genet Cytogenet 19:281-289. 4. Seabright M (1971): A rapid banding technique for human chromosomes. Lancet 2:971-972. 5. ISCN (1978): An International System for Human Cytogenetic Nomenclature. (1978). Birth Defects: Original Article Series, Vol. XIV, No. 8. (The National Foundation, New York, 1978); also in Cytogenet Cell Genet 21:304-404. 6. Bloomfield CD (1986): Chromosome abnormalities in secondary myelodysplastic syndromes. Scand J Haematol 45(Suppl):82-90.