Inversion of Chromosome 16 and Bone Marrow Eosinophilia in a Myelomonocytic Transformation of Chronic Myeloid Leukemia Norio Asou, Isao Sanada, Kenji Tanaka, Michihiro Hidaka, Hitoshi Suzushima, Hiromitsu Matsuzaki, Fumio Kawano, and Kiyoshi Takatsuki
A B S T R A C T : We report a case of chronic myeloid leukemia (CML) in m y e l o m o n o c y t i c transformation
associated with bone marrow (BM) eosinophilia. A t diagnosis, all BM cells showed a Ph chromosome. A t the time of blastic phase, more than 50% of Ph ÷ cells had a pericentric inversion of c h r o m o s o m e 16, inv(16)(p13q22). This case confirms that blastic transformation of CML can involve any c o m m i t t e d progenitor, and m y e l o m o n o c y t i c leukemia with BM eosinophilia is specifically associated with rearrangement of c h r o m o s o m e 16 at band p13 and q22.
INTRODUCTION Most patients with chronic myeloid leukemia (CML) develop blastic phase associated with considerable variability of clinical features and short survival [1]. CML is a clonal disease originating from the pluripotent stem cell, and the blastic transformation can affect any one or more of the committed progenitors [2, 3]. The heterogeneity of the cell populations involved in the blastic phase can now be defined more precisely by immunophenotypic analysis [3]. Additional chromosome changes in Ph ÷ cells are observed in more than 70% of patients at blastic phase [4, 5]. However, specific abnormalities first identified in acute leukemias are rarely noted [6, 7]. Except for the t(15;17) specifically associated with acute promyelocytic leukemia, which has been observed in patients with promyelocytic transformation of CML [8, 9]. The t(8;21) in Ph ÷ cells was also observed in one patient with CML blastic phase [10]. In addition, Ph ÷ cells from cases of CML blastic phase associated with abnormal thrombopoiesis showed the karyotypic changes involving 3q26 and/or 3q21 associated with acute myeloid leukemia (AML) with abnormal megakaryocytopoiesis [11, 12]. Association of acute myelomonoblastic leukemia with bone marrow (BM) eosinophilia, designated M4Eo by the
From the Second Department of Internal Medicine, Kumamoto University Medical School (N. A., K. T., M. H., H. S., H. M.), and Internal Medicine, Kumamoto National Hospital (I. S., F. K.), Kumamoto, Japan. Address reprint requests to: tsao Sanada, M.D., Internal Medicine, Kumamoto National Hospital, 1-5 Ninomaru, Kumamoto 860, Japan. Received October 15, 1990; accepted March 3, 1992. © 1992 Elsevier Science Publishing Co.. Inc.
655 Avenue of the Americas.New York. NY 10010
French-American-British (FAB) Cooperative Group [13], and inv(16) or t(16;16) is well documented [14-17]. To our knowledge, the M4Eo form of blastic phase in CML has never been reported. We report a case of M4Eo type of blastic transformation with inv(16) in Ph ÷ CML.
CASE REPORT
A 51-year-old man was referred to our hospital in November 1986 because of splenomegaly and leukocytosis. He had a 2-week history of low-grade fever, abdominal fullness, left hypochondralgia, and a 10-ks weight loss in the 2 years before admission. Physical examination showed pallor and splenomegaly 13 cm below the costal margin. The hemoglobin (Hb) level was 10.9 g/dl, and the platelet count was 362 x 109/L. The leukocyte count was 314.4 x 109/L, with a differential of 2% blasts, 26% promyelocytes, 2% metamyelocytes, 55% neutrophils, 5% basophils, 1% eosinophils, 7% lymphocytes, and two erythroblasts per 100 white blood cells (WBC). The BM aspirate was hypercellular with 10.4% blasts, 28% promyelocytes, 5% myelocytes, 37% neutrophits, 7.8% eosinophils, 0.6% lymphocytes, 0.6% monocytes, and 0.4% erythroblasts. Blood chemistry showed normal results except for an elevated lactate dehydrogenase of 816 U/L. The leukocyte alkaline phosphatase score was 67 (normal range 170-367). A diagnosis of CML in accelerated phase was made, and the patient received busulfan therapy for 1 month with no response. In December 1986, hematologic findings were indicative of blastic phase of CML (Table 1). The leukocyte count increased to 560 x 109/L with 8% blastic cells. Bone marrow aspirate showed 22.4% blasts, 20.4% promyelocytes, 197 Cancer Genet Cytogenet61:197-200 (1992) 0165-4608/92/$05.00
198
N. A s o u et al.
Table 1 Cytogenetic and clinical data of bone marrow samples Date of sampling
Clinical status
Blasts (%)
Promonocytes (%)
Abnormal eosinophils (%)
No. of metaphases
No. of karyotypes
11/12/86
10.4
0.8
1.8
19
19
12/1/86
Accelerated phase Blastic phase
22.4
7.6
8.2
21
9/12
1/14/87 2/13/87
Blastic phase Blastic phase
50.8 9.2
21.2 44.8
16.8 3.6
46
1/20/14/3/8
5.2% promonocytes, 2.4% monocytes, and 12.2% eosinophils. Some e o s i n o p h i l s (8.2%) had a single nucleus and large b a s o p h i l i c granules a d m i x e d with granules of normal appearance (Fig. 1). The blasts were positive for myeloperoxidase staining (71%) and for either chloroacetate (27%) or butyrate esterase (35%). The eosinophils were positive for myeloperoxidase, chloroacetate esterase, and periodic acid-Schiff. The l y s o z y m e concentration was increased in the serum to 110/zg/ml (3.0-10.6/zg/ml) and in the urine to 710/zg/ml (
A B S T R A C T : We report a case of chronic myeloid leukemia (CML) in m y e l o m o n o c y t i c transformation
associated with bone marrow (BM) eosinophilia. A t diagnosis, all BM cells showed a Ph chromosome. A t the time of blastic phase, more than 50% of Ph ÷ cells had a pericentric inversion of c h r o m o s o m e 16, inv(16)(p13q22). This case confirms that blastic transformation of CML can involve any c o m m i t t e d progenitor, and m y e l o m o n o c y t i c leukemia with BM eosinophilia is specifically associated with rearrangement of c h r o m o s o m e 16 at band p13 and q22.
INTRODUCTION Most patients with chronic myeloid leukemia (CML) develop blastic phase associated with considerable variability of clinical features and short survival [1]. CML is a clonal disease originating from the pluripotent stem cell, and the blastic transformation can affect any one or more of the committed progenitors [2, 3]. The heterogeneity of the cell populations involved in the blastic phase can now be defined more precisely by immunophenotypic analysis [3]. Additional chromosome changes in Ph ÷ cells are observed in more than 70% of patients at blastic phase [4, 5]. However, specific abnormalities first identified in acute leukemias are rarely noted [6, 7]. Except for the t(15;17) specifically associated with acute promyelocytic leukemia, which has been observed in patients with promyelocytic transformation of CML [8, 9]. The t(8;21) in Ph ÷ cells was also observed in one patient with CML blastic phase [10]. In addition, Ph ÷ cells from cases of CML blastic phase associated with abnormal thrombopoiesis showed the karyotypic changes involving 3q26 and/or 3q21 associated with acute myeloid leukemia (AML) with abnormal megakaryocytopoiesis [11, 12]. Association of acute myelomonoblastic leukemia with bone marrow (BM) eosinophilia, designated M4Eo by the
From the Second Department of Internal Medicine, Kumamoto University Medical School (N. A., K. T., M. H., H. S., H. M.), and Internal Medicine, Kumamoto National Hospital (I. S., F. K.), Kumamoto, Japan. Address reprint requests to: tsao Sanada, M.D., Internal Medicine, Kumamoto National Hospital, 1-5 Ninomaru, Kumamoto 860, Japan. Received October 15, 1990; accepted March 3, 1992. © 1992 Elsevier Science Publishing Co.. Inc.
655 Avenue of the Americas.New York. NY 10010
French-American-British (FAB) Cooperative Group [13], and inv(16) or t(16;16) is well documented [14-17]. To our knowledge, the M4Eo form of blastic phase in CML has never been reported. We report a case of M4Eo type of blastic transformation with inv(16) in Ph ÷ CML.
CASE REPORT
A 51-year-old man was referred to our hospital in November 1986 because of splenomegaly and leukocytosis. He had a 2-week history of low-grade fever, abdominal fullness, left hypochondralgia, and a 10-ks weight loss in the 2 years before admission. Physical examination showed pallor and splenomegaly 13 cm below the costal margin. The hemoglobin (Hb) level was 10.9 g/dl, and the platelet count was 362 x 109/L. The leukocyte count was 314.4 x 109/L, with a differential of 2% blasts, 26% promyelocytes, 2% metamyelocytes, 55% neutrophils, 5% basophils, 1% eosinophils, 7% lymphocytes, and two erythroblasts per 100 white blood cells (WBC). The BM aspirate was hypercellular with 10.4% blasts, 28% promyelocytes, 5% myelocytes, 37% neutrophits, 7.8% eosinophils, 0.6% lymphocytes, 0.6% monocytes, and 0.4% erythroblasts. Blood chemistry showed normal results except for an elevated lactate dehydrogenase of 816 U/L. The leukocyte alkaline phosphatase score was 67 (normal range 170-367). A diagnosis of CML in accelerated phase was made, and the patient received busulfan therapy for 1 month with no response. In December 1986, hematologic findings were indicative of blastic phase of CML (Table 1). The leukocyte count increased to 560 x 109/L with 8% blastic cells. Bone marrow aspirate showed 22.4% blasts, 20.4% promyelocytes, 197 Cancer Genet Cytogenet61:197-200 (1992) 0165-4608/92/$05.00
198
N. A s o u et al.
Table 1 Cytogenetic and clinical data of bone marrow samples Date of sampling
Clinical status
Blasts (%)
Promonocytes (%)
Abnormal eosinophils (%)
No. of metaphases
No. of karyotypes
11/12/86
10.4
0.8
1.8
19
19
12/1/86
Accelerated phase Blastic phase
22.4
7.6
8.2
21
9/12
1/14/87 2/13/87
Blastic phase Blastic phase
50.8 9.2
21.2 44.8
16.8 3.6
46
1/20/14/3/8
5.2% promonocytes, 2.4% monocytes, and 12.2% eosinophils. Some e o s i n o p h i l s (8.2%) had a single nucleus and large b a s o p h i l i c granules a d m i x e d with granules of normal appearance (Fig. 1). The blasts were positive for myeloperoxidase staining (71%) and for either chloroacetate (27%) or butyrate esterase (35%). The eosinophils were positive for myeloperoxidase, chloroacetate esterase, and periodic acid-Schiff. The l y s o z y m e concentration was increased in the serum to 110/zg/ml (3.0-10.6/zg/ml) and in the urine to 710/zg/ml (
