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A further case of Philadelphia chromosome-positive chronic myeloid leukemia with t(3;9;22)
LETTERS TO THE EDITOR A Further Case of Philadelphia Chromosome-Positive Chronic Myeloid Leukemia with t(3;9;22)
We present a report of a further case of chronic m y e l o i d l e u k e m i a (CML) w i t h a variant P h i l a d e l p h i a (Ph) c h r o m o s o m e translocation. T. S., a 24-year-old male, was seen at the Oshawa General Hospital for progres-
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F i g u r e 1 Partial karyotype s h o w i n g t(3;9;22) (p25;q34;q11).
Received May 26, 1988; accepted June 10, 1988. 279
© 1988 Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York. NY 10010
Cancer Genet Cytogenet 35:279-280 (1988) 0165-4608/88/$03.50
280
M. De Braekeleer et al.
sive weakness and increasing tiredness of 1 m o n t h ' s duration. Physical examination revealed a splenomegaly 4 cm below the costal margin, with no hepatomegaly or peripheral l y m p h node enlargement. Laboratory tests showed the hemoglobin at 108 g/L, red blood cell count 3.3 x 1012/L, white blood celt count 147.6 x 109/L with a differential count of 0.50 granulocytes, 0.08 bands, 0.07 metamyelocytes, 0.17 myelocytes, 0.05 promyelocytes, 0.01 blasts, 0.03 basophils, 0.01 eosinophils, and 0.06 lymphocytes. The platelet count was 419 x 109/L. Bone marrow examination showed a hypercellular bone marrow due to proliferation of the myeloid line with a myelocytic and promyelocytic hump. A diagnosis of CML was made, and chemotherapy with hydroxyurea (2 mg/day) was started. Chromosomes of bone marrow cells were analyzed immediately after collection. G b a n d i n g was performed by the t r y p s i n - G i e m s a method (GTG), and the karyotype was arranged according to the recommendations of the ISCN [1]. A t(3;9;22) (p25;q34;q11) was seen in all 20 cells examined (Fig. 1). The patient responded to high-dosage hydroxyurea given orally. The spleen regressed, blood counts returned to near-normal levels, and the patient remains stable 7 months later. Thirty-five variant Ph translocations involving chromosome 3 have now been reported in CML. The short arm (3p) was involved in 21 cases, with breakpoints at band 3p21 16 times, at band 3p13 four times, and at b a n d 3p23 once. TO ttie best of our knowledge, this is the first time that band 3p25 was found to be rearranged in a variant Ph translocation in CML. Although it has been shown that CML patients with a variant Ph translocation have the same laboratory, clinical, and prognostic features as those with the standard t(9;22) [2], reporting new cases of variant Ph translocations may help us u n d e r s t a n d the mechanisms of chromosome breakage in leukemia. Indeed, the protooncogene c-raf-1 is mapped to band 3p25 [3] and, therefore, could have facilatated breakage. The authors thank Kim Mellick and Joan Halbgewachs for excellent technical assistance. MARC DE BRAEKELEER
HAK-MING CHIU JARMILA FISER H. ALLEN GARDNER
SOREP Department of Human Sciences University of Quebec at Chicoutimi 555 Blvd. de 1' Universite Chicoutimi, Quebec G7H 2B1 Canada
Oshawa General Hospital Oshawa, Ontario LIG 2B9 Canada
REFERENCES
1. 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 21:309-344 (1978). 2. De Braekeleer M (1987): Variant Philadelphia translocations in chronic myeloid leukemia. Cytogenet Cell Genet 44:215-222. 3. Human Gene Mapping 8 (1985): Eighth International Workshop on Human Gene Mapping, Helsinki. Cytogenet Cell Genet 40:1-535.
We present a report of a further case of chronic m y e l o i d l e u k e m i a (CML) w i t h a variant P h i l a d e l p h i a (Ph) c h r o m o s o m e translocation. T. S., a 24-year-old male, was seen at the Oshawa General Hospital for progres-
~:~i!!!¸iii: ! ! i!i : : :
: :¸
iiii,~iil iii!~i:i, ~i': i
¸¸
F i g u r e 1 Partial karyotype s h o w i n g t(3;9;22) (p25;q34;q11).
Received May 26, 1988; accepted June 10, 1988. 279
© 1988 Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York. NY 10010
Cancer Genet Cytogenet 35:279-280 (1988) 0165-4608/88/$03.50
280
M. De Braekeleer et al.
sive weakness and increasing tiredness of 1 m o n t h ' s duration. Physical examination revealed a splenomegaly 4 cm below the costal margin, with no hepatomegaly or peripheral l y m p h node enlargement. Laboratory tests showed the hemoglobin at 108 g/L, red blood cell count 3.3 x 1012/L, white blood celt count 147.6 x 109/L with a differential count of 0.50 granulocytes, 0.08 bands, 0.07 metamyelocytes, 0.17 myelocytes, 0.05 promyelocytes, 0.01 blasts, 0.03 basophils, 0.01 eosinophils, and 0.06 lymphocytes. The platelet count was 419 x 109/L. Bone marrow examination showed a hypercellular bone marrow due to proliferation of the myeloid line with a myelocytic and promyelocytic hump. A diagnosis of CML was made, and chemotherapy with hydroxyurea (2 mg/day) was started. Chromosomes of bone marrow cells were analyzed immediately after collection. G b a n d i n g was performed by the t r y p s i n - G i e m s a method (GTG), and the karyotype was arranged according to the recommendations of the ISCN [1]. A t(3;9;22) (p25;q34;q11) was seen in all 20 cells examined (Fig. 1). The patient responded to high-dosage hydroxyurea given orally. The spleen regressed, blood counts returned to near-normal levels, and the patient remains stable 7 months later. Thirty-five variant Ph translocations involving chromosome 3 have now been reported in CML. The short arm (3p) was involved in 21 cases, with breakpoints at band 3p21 16 times, at band 3p13 four times, and at b a n d 3p23 once. TO ttie best of our knowledge, this is the first time that band 3p25 was found to be rearranged in a variant Ph translocation in CML. Although it has been shown that CML patients with a variant Ph translocation have the same laboratory, clinical, and prognostic features as those with the standard t(9;22) [2], reporting new cases of variant Ph translocations may help us u n d e r s t a n d the mechanisms of chromosome breakage in leukemia. Indeed, the protooncogene c-raf-1 is mapped to band 3p25 [3] and, therefore, could have facilatated breakage. The authors thank Kim Mellick and Joan Halbgewachs for excellent technical assistance. MARC DE BRAEKELEER
HAK-MING CHIU JARMILA FISER H. ALLEN GARDNER
SOREP Department of Human Sciences University of Quebec at Chicoutimi 555 Blvd. de 1' Universite Chicoutimi, Quebec G7H 2B1 Canada
Oshawa General Hospital Oshawa, Ontario LIG 2B9 Canada
REFERENCES
1. 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 21:309-344 (1978). 2. De Braekeleer M (1987): Variant Philadelphia translocations in chronic myeloid leukemia. Cytogenet Cell Genet 44:215-222. 3. Human Gene Mapping 8 (1985): Eighth International Workshop on Human Gene Mapping, Helsinki. Cytogenet Cell Genet 40:1-535.