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Cancer Genet Cytogenet 100:152–155 (1998)

Elsevier Science Inc., 1998655 Avenue of the Americas, New York, NY 10010

Translocation (5;10)(q13;q26) in Acute Monoblastic Leukemia

Francesco Pernice, Caterina Musolino, Giuseppa Mazza, Domenico Puglisi, Giovanni Squadrito, Nicola Frisina, and Giuseppe Squadrito

ABSTRACT:

We report a case of acute monoblastic leukemia [French-American-British (FAB) M5a]observed in a 38-year-old man and associated at diagnosis with a t(5;10)(q13;q26) found in cells from abone marrow culture. The patient survived only 2 months after diagnosis. t(5;10) as a solitary chromo-some abnormality has not been previously reported in M5a, and, in the case that we describe, it appearsto be correlated with a poor prognosis. © Elsevier Science Inc, 1998

INTRODUCTION

Several nonrandom chromosomal abnormalities have beendescribed in hematologic disorders and correlated withthe clinical picture and the course of the disease. Specificchromosomal abnormalities have been reported in about50% of acute nonlymphocytic leukemias (ANLL) andassociated with the different morphological and clinicalsubtypes, classified according to the French-American-British proposals (FAB) [1]. These chromosomal changesinclude trisomy 8 (8

1

) in acute myeloblastic leukemiawithout maturation (FAB M1); t(8;21)(q22;q22) in acutemyeloblastic leukemia (FAB-M2); t(15;17)(q22;q21) exclu-sively associated with acute promyelocytic leukemia(FAB-M3); and rearrangements of chromosome 16 in acutemyelomonocytic leukemia (FAB M4) [2].

Nonrandom chromosomal rearrangements have beenreported in acute monoblastic leukemia (FAB M5), andsome cytogenetic aberrations have been preferentially as-sociated with subtypes M5a and M5b; del(11)(q23) andt(9;11)(p21;q23) in M5a [3, 4] and t(8;16)(p11;p13) in M5b[5, 6].

We report a case of acute monoblastic leukemia FABM5a with the occurrence of t(5;10)(q13;q26) as a solitarychromosome abnormality in bone marrow culture.

MATERIALS AND METHODS

Patient

A 38-year-old man was admitted in 1986 to the Institute ofInternal Medicine, Messina, because of weakness, fever,and bleeding from the gums during the preceding 2 weeks.At physical examination, the liver, spleen, and peripherallymphonodes were moderately enlarged. Hematologic lab-oratory findings were: hemoglobin 10.3 g/dL; white bloodcells 75

3

10

9

/L with 22% neutrophils, 12% lymphocytes,2% band forms, 3% monocytes, 30% promonocytes, and31% monoblasts; platelets 40

3

10

9

/L. The serum concen-tration of lysozyme was elevated to 25 mg/L. Bone marrowaspiration showed 80% blast cells. Cytochemical investi-gations of the leukemic blasts revealed a pattern of smalldiffuse positivity when stained with periodic acid–Schiffand strong positivity with alpha-naphthyl acetate esterase.The positive reaction with esterase was inhibited bysodium fluoride. Immunological studies with monoclonalantibodies showed that the cells were positive for CD14,HLA-DR, and CD11c and negative for CD33, CD13, CD20,CD21, CD10, CD5, and CD7. A diagnosis of acute mono-cytic leukemia, M5a according to the FAB classification,was made. Treatment with cytosine-arabinoside and dauno-mycin was started, and partial remission was achieved.Then a second phase of induction chemotherapy wasstarted with etoposide, oral 6-thioguanine, cytosine arabi-noside, daunomycin, and dexamethasone. A bone marrowaspirate at the end of the second course of chemotherapyrevealed a partial remission again. However, at that time,the patient developed high fever and abdominal pain, wasseverely leukopenic, and failed to respond to treatmentwith antibiotics. He died from septicemia 2 months afterdiagnosis.

From the Cattedra e Divisione di Medicina Interna (N. F., F. P.,C. M., D. P.) and the Dipartimento di Medicina Interna e TerapiaMedica (Gio. S., G. M., Giu. S.), Università degli Studi di Messina,Messina, Italy.

Address reprint requests to: Dr. Francesco Pernice, Cattedra eDivisione di Medicina Interna, Policlinico Universitario GaetanoMartino, 98100 Messina, Italy.

Received January 8, 1997; accepted June 18, 1997.

t(5;10) in AML M5a

153

Figure 1 G-banded metaphase and karyotype of bone marrow cell: 46,XY,t(5;10)(q13;q26).

154

F. Pernice et al.

Cytogenetic Methods

Chromosome studies were performed on 48-hour and 72-hour unstimulated cultures of a bone marrow aspirate.

Heparinized bone marrow sample was washed in RPMI-1640 medium. Cells were cultured in RPMI medium sup-plemented with 20% fetal calf serum, penicillin (200units/mL), and streptomycin (200

m

g/mL).After 48 hours and 78 hours, methotrexate at a final con-

centration of 10-7 M was added for 17 hours. Then, theculture medium was changed and 5BrdU, at a final con-centration of 15

m

g/mL, was added for 5 hours. Cells werearrested in metaphase by addition of colchicine at finalconcentration of 0.1

m

g/mL for 30

to

60 min.Hypotonic treatment was performed with 0.075 M po-

tassium chloride and the cells fixed in cold methanol–gla-cial acetic acid (3:1). Glass slides obtained were air dried.Metaphases were studied by GBG (Fig. 1) and RBG (Fig. 2)banding techniques, which include the use of trypsin andGiemsa for G bands and the use of Bisbensamid for Rbands. Karyotypes were classified on the basis of the ISCNnomenclature [7].

RESULTS AND DISCUSSION

Chromosome analysis of bone marrow cells was per-formed to obtain a better characterization of the diagnosis.

Figure 2 R-banded karyotype of bone marrow cell: 46,XY,t(5;10)(q13;q26).

Figure 3 Partial selected karyotype of chromosome pairs 5 and10, showing t(5;10)(q13;q26) by G and R banding.

t(5;10) in AML M5a

155

Thirty metaphases were studied and, in all of them, ourexamination revealed the following karyotype: t(5;10)(q13;q26) (Fig. 3).

M5 acute monocytic or monoblastic leukemia (AML)has been divided into M5a, the less-frequent and undiffer-entiated subtype associated with a high percentage ofpoorly differentiated cells, and M5b, in which fewer than20% of the monocytic cells are monoblasts.

Nonrandom chromosomal rearrangements have beenobserved in AML (M5) and preferentially associated withsubtypes M5a or M5b. Translocation (8;16)(p11;p13) hasbeen reported as being associated with monocytic sub-types of acute nonlymphocytic leukemia, particularly(M5) and specifically with subtype M5b. This transloca-tion has been correlated with evidence of erythrophago-cytosis and extramedullary disease [5, 6, 8]. Berger et al.[9] first reported the high frequency of 11q rearrange-ment in M5 patients. A specific translocation involvingchromosome 9 and the long arm of chromosome 11, withthe breakpoint at q23,t(9;11)(p21;q23)[4], t(9;11)(p22;q23),was observed and closely associated with M5a subtype[10–14].

Anomalies involving chromosome 5 are not frequentlyreported in de novo ANLL. In a study on 660 patients withde novo ANLL, these anomalies were observed in 4.2% ofcases [2]. The most frequent abnormality of chromosome 5observed is

2

5 or 5q

2

, and the association of 5q

2

chromo-some and refractary anemia was first reported by van denBerg et al. [15].

In 5q

2

, the proximal breakpoint is commonly locatedin 5q13–5q15 and the distal breakpoint in 5q33. This 5qanomaly in ANLL may be included in 5q

2

syndrome andis characterized by the deletion of genetic material with-out translocation and the loss of the deleted material.

Chromosomal rearrangements including the transloca-tion of genetic material of chromosome 5 to others chro-mosomes have not been frequently described in de novoANNL, and the translocation (5;10) has rarely been re-ported. Kaneko et al. reported a translocation (5;10)(q35;q23 or q24) in a 2-year-old child with acute myelomono-cytic leukemia (M4) [11]. To our knowledge, the transloca-tion (5;10)(q13;q26) has never been described in de novoANLL and is a new chromosomal rearrangement associatedwith AML M5a. The breakpoint in 5q in the case that we de-scribe is located in the segment involved in 5q

2

syndrome.Both the clinical course of the disease and the patient’s

death 2 months after diagnosis suggest that this chromo-some aberration may be correlated with a poor prognosis.A third feature, which may be associated with t(5;10), isthe resistance of this form of leukemia to a heavy and ag-gressive antiblastic chemotherapy, as reported in the pa-

tient description. However, the meaning of this chromosomeaberration will be further clarified when additional caseshave been described and cytogenetic studies carried out.

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