Loss of band 13q14 in a myelodysplastic syndrome

Loss of Band 13q14 in a Myelodysplastic Syndrome Band 13q14 is thought to be important in the genesis of either the sporadic or hereditary form of retinoblastoma. An interstitial deletion of the long arm of chromosome #13, involving loss of band 13q14, recently has been described as a primary karyotypic change in preleukemia [1]. Furthermore, a specific association of 1 3 q with myelofibrosis has been suggested [2, 3]. We observed an interstitial deletion of chromosome #13, involving band 13q14, in a case of myelodysplastic syndrome (MDS). The patient was a 62oyear-old man referred to our hospital in June 1982 because of severe anemia. His spleen and liver were not enlarged. The hematologic picture was as follows: hemoglobin 5.8 gr/dl, mean corpuscular volume 108 fl, leukocytes 5.1 x 109/L (neutrophils 22%, lymphocytes 55%, monocytes 15%, myelocytes 2%, metamyelocytes 6%) and platelets 44 × 109/L. Erythroblasts were present in the peripheral smear. The bone marrow examination showed a marked increase in the red cell series, with dyserythropoietic features, such as macrocytosis, binuclearity, basophilic stippling, and ringed sideroblasts (10%). Myeloblasts represented 3% of the white cells. Serum levels of vitamin B12 and folic acid were normal. The patient had no history of myelofibrosis or agnogenic myeloid metaplasia. A diagnosis of refractory anemia was made according to the FAB classification, and therapy with red cell transfusions was started. In the following months the clinical and hematologic picture remained stable until November 1984, when melena appeared. At that time the erythroid series represented 78% of bone marrow cells; blasts were 28% of the myeloid lineage. The peripheral blood leukocytes were 2.1 x 109/L, 20% of which were blasts; many erythroblasts were also observed. Platelets were 14 x 1 0 9 / L . A diagnosis of refractory anemia with excess of blasts in transformation (RAEB-t) was made, and treatment with low-dose cytosine-arabinoside was administered. However, no improvement was observed and the patient died in January 1985 of Candida sepsis; at that time the peripheral blood showed features of acute myelogenous leukemia with 50% myeloblasts. Chromosome studies were performed in September 1984 on bone marrow cells after 48 hours of unstimulated culture; metaphases were analyzed after Q-banding. Two different subclones were observed: 47,XY,del(13)(q12q14),+21 in 22 of 31 cells and 48,XY,del(13)(q12q14), + del(13)(q12q14), + 21 in the remaining nine cells (Fig. la and b). Peripheral lymphocytes stimulated with PHA and G-banded revealed a normal male karyotype 46,XY (Fig. lc). In our patient two cytogenetic abnormalities, namely 1 3 q - and trisomy 21, were observed; moreover a duplication of the deleted chromosome #13 was found in 29% of the bone marrow cells. The presence of two subclones is consistent with a karyotypic evolution during the progression of the hematologic disorder from refractory anemia to RAEB-t and further to frank leukemia. Two cases of 1 3 q - in MDS have been reported by Johnson [4]. However, 1 3 q cannot be considered a specific rearrangement in MDS, because it has also been described in a number of patients with polycythemia vera, either in chronic phase or in evolution to myelofibrosis [4, 5] as well as in primary myelofibrosis [2, 3]. It is noteworthy that in our case, as in other patients previously reported [1, 4], progression of the disease is characterized by chromosomal abnormalities in addition

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Cancer Genet Cytogenet 28:181-18211987) 0165-4608/87/$03.50

F i g u r e 1 Q-banded partial karyotypes showing the deletion of the long arm of chromosome #13 (a) and its duplication (b), both associated with trisomy 21. In (c), normal G-banded chromosomes #13 and #21 from PHA-stimulated lymphocytes are shown.

to 1 3 q - . It has b e e n s h o w n that 13q may be a p r i m a r y step in p r e l e u k e m i c syndromes, a c c o m p a n i e d by a d d i t i o n a l c h r o m o s o m e c h a n g e s at the t i m e of p r o g r e s s i o n to acute l e u k e m i a [1]. In our case, therefore, 1 3 q - m i g h t r e p r e s e n t the first karyo t y p i c c h a n g e in a refractory anemia. T h e p r e s e n c e of t r i s o m y 21 is in k e e p i n g with this h y p o t h e s i s as this a b n o r m a l i t y f r e q u e n t l y o c c u r s as an a d d i t i o n a l c h r o m o s o m a l c h a n g e in M D S e v o l v i n g t o w a r d s acute l e u k e m i a (6]. This work was supported in part by MP60% and CNR, Rome, Special Project "Oncotogy". GIORGIO PONZIO GIOVANNA REGE-CAMBRIN GIORGIO NERETTO

Institute of Medical Genetics University of Turin, Italy Department of Biomedical Sciences and Human Oncology University of Turin, Italy Division of Hematology Ospedale Mauriziano, Turin, Italy

REFERENCES 1. Morgan R, Hecht F (1985): Deletion of chromosome band 13q14: A primary event in preleukemia and leukemia. Cancer Genet Cytogenet 18:243-249. 2. Borgstrom GH, Knuutila S, Ruutu T, Pakkala A, Lahtinen R, de la Chapelle A (1984): Abnormalities of chromosome 13 in myelofibrosis. Scand J Hematol 33:15-21. 3. Carbone P, Barbata G, Mirto S, Marceno R, Leone S, Granata G (1984): Cytogenetic studies in five patients with myelofibrosis and myeloid metaplasia. Cancer Genet Cytogenet 6:213221. 4. Johnson DD, Dewald GW, Pierre RV, Letendre L, Silverstein MN (1985): Deletions of chromosome 13 in malignant hematological disorders. Cancer Genet Cytogenet 18:235-241. 5. Rege-Cambrin G, Mecucci C, Tricot G, Michaux JL, Lowagie A, Van Hove W, Francart H, Van Den Berghe H (1987): A chromosomal profile of polycythemia vera. Cancer Genet Cytogenet (in press) 6. Van Den Berghe H, Vermaelen K, Mecucci C, Barbieri D, Tricot G, (1985): The 5 q - anomaly. Cancer Genet Cytogenet 17:189-225.