Letter to the editor: A case of chronic myelocytic leukemia with five Philadelphia chromosomes

Letter to the Editor: A Case of Chronic Myelocytic Leukemia with Five Philadelphia Chromosomes The letter of Gibas et al. [1] on a case of chronic myelogenous leukemia (CML) with four Philadelphia chromosomes (Ph) prompts us to report a case in the blastic phase of CML with a cell line with five copies of the Ph chromosome. The patient, D.S., a male, was born in 1950 and a diagnosis of CML was made in 1975. He presented with liver and spleen enlargement and laboratory data were: WBC 51,900/mm 3 with 53% neutrophils, 1% basophils, 7% lymphocytes, 1% monocytes, 13% metamyelocytes, 20% myelocytes, 4% promyelocytes, 1% myeloblasts; platelets 210,000/mm 3, leukocyte alkaline phosphatase (LAP) score 4 (n.v. 90-+ 50). The karyotype showed the presence of the Ph with a standard translocation (Table 1). The patient was treated with busulfan with good results and he remained in stable chronic phase until 1984. In February 1984 splenomegaly reappeared and the WBC increased to 33,700/ m m 3 with 45% neutrophils, 3% eosinophils, 2% basophils, 7% lymphocytes, 7% metamyelocytes, 7% myelocytes, 1% promyelocytes, 28% myeloblasts; platelets 86,000/ram a. The bone marrow showed hyperplasia of the myeloid series with preponderant eosinophilic ceils. Blasts were mostly PAS-negative and Sudan-positive. The LAP score was 4. This accelerated phase of the disease led to an overt blastic phase in March 1984, when the WBC reached 80,000/mm 3. The patient u n d e r w e n t spleen irradiation and courses of therapy with hydroxyurea, and slight improvement was obtained. The WBC in April 1984 was 15,700/mm 3. Later, the patient's condition rapidly deteriorated and he died in April 1984. The chromosome analyses performed with Q-, G-, and C-banding techniques during blastic phase showed some additional anomalies; i n c l u d i n g loss of the Y Table 1 Date 6/9/75 2/22/84 3/28/84

4/17/84

"Ph

Results of chromosome analyses on u n s t i m u l a t e d blood cultures Number of cells

Karyotype

10 5 5 20 8 7 17 1 1 1

46,XY,t(9;22)(q34;q11) 45,X,- Y, 17, + der(1)t(1;17)(p11;q11),t(9;22)(q34;q11) 48,X,- Y,- 17, + der(1)t(1;17)(p 11;q11),t(9;22)(q34;q11), + 3Ph" 45,X, Y, - 17, + der(1)t(1;17)(p11;qll),t(9;22](q34;q11) 48,X, - Y, - 17, + der(1]t[1;17)(pll ;qll),t(9;22)(q34;q11 ), + 3Ph" 49,X, - Y,- 17, + der(1)t(1 ;17){pl 1:q1"l),t(9;22)(q34;ql 1), + 4Ph" 45,X, Y, - 17, + der(1)t(1;17)(p11;qll),t(9;22)(q34;q11) 48,X, - Y,- 17, + der(1)t(1;17)(p11;ql 1),t{9;22)(q34;q11),+ 3Ph" 49,X, - Y, - 17, + der(1)t(1;17)(p11;qll),t(9;22)(q34;q11), + 4Ph" 46,XY,t(9;22)(q34;q11)

= der(22)t(9;22)(q34:q11}.

Received February 19, 1988; accepted April 13, 1988.

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Cancer Genet Cytogenet34:257 259 (1988] 0165-4608/88/$03.50

258

•. Casalone and E. Maserati

Figure 1 A Q-banded metaphase showing five copies of the Ph-chroFI1OSOFII e .

chromosome, an u n b a l a n c e d translocation between chromosomes #1 and #17, and the presence of four or five copies of the Ph in different cell lines (Table 1; Fig. 1). Some comments are appropriate. 1. We did not find any other case in the literature with a cell line with five copies of the Ph. Among 139 cases of CML in blastic phase studied in our laboratory in the period 1971-1985, a duplication of the Ph was present in 28, but only the patient reported here had more than two Ph. 2. Gibas et al. [1] correlated the proportion of cells with multiple copies of the Ph with the remission of the blastic phase. Our patient never entered a real remission phase, but the clones with four and five Ph appeared to have a lower mitotic activity w h e n the therapy had some effect, and the WBC decreased to 15,700/ m m 3. 3. The u n b a l a n c e d t(1;17) of this case is identical to that of a patient with CML in blastic phase that we reported a few years ago [2]. A high proportion of eosinophilic cells in the bone marrow was a sign c o m m o n to both cases. 4. A correlation between structural anomalies of a #17 and an acquired pseudoPelger-Huet a n o m a l y in CML was recently postulated [3]. In fact, our patient had 30% pseudo-Pelger-Huet neutrophils in his peripheral blood. This work was supported by Grant no. 87.01290.44 from CNR, Progetto Finalizzato oncologia. R. CASALONE E. MASERATI

Biologia Genera|e e Genetica Medica University of Pavia C.P. 217 1-27100 Pavia, Italy

CML a n d F i v e Ph C h r o m o s o m e s

259

REFERENCES 1. Gibas L, Jackson L, Fellin MF (1987): A case of chronic myelogenous leukemia with four Philadelphia chromosomes. Cancer Genet Cytogenet 28:179-180. 2. Pasquali F, Francesconi D, Casalone R, Ippoliti G (1979): Partial trisomy 1 due to 1/17 translocation in Phi-positive chronic myelocytic leukemia. Hum Genet 49:277-282. 3. Sessarego M, Ajmar F (1987): Correlation between acquired pseudo-Pelger Huet anomaly and involvement of chromosome 17 in chronic myeloid leukemia. Cancer Genet Cytogenet 25:265-270.