Translocation 8;21 Associated with Acute

Nonlymphocytic Leukemia in a Down Syndrome Child

Erzs bet Balogh, l va Ol h, and Katalin Hunyadi

ABSTRACT: A boy with Down syndrome who developed acute nonlymphocy'tic leukemia (ANLL/M2) at the age of 40 months is presented. Chromosomal analysis of cultured peripheral blood cells without mitogen revealed a constitutional abnormality, trisomy 21, associated with the acquired chromosome change t(8;21)(q22;q22).

INTRODUCTION

We report a unique case of acute nonlymphocyt ic leukemia in a child with Down syndrome. Cytogenetic analysis of leu- kemic ceils showed that the translocation t(8;21)(q22;q22) superimposed on the constitutional trisomy 21. To our knowledge this association has been reported only once in an adult patient [1].

CASE REPORT

Sz. D. was born to young and healthy parents following an uneventful pregnancy. Birth weight was 3500 g. There were no perinatal complications. Down syndrome was suspected after the birth on the basis of physical examination (brachy- cephaly, flat profile, epicanthus, small nose, large tongue). Karyotyping justified trisomy 21 in all the examined cells. At age of 3.5 years he was referred to the hospital with a 5-week history of fever, cough, pallor, and hepatospleno- megaly. Initial peripheral blood showed the hemoglobin was 5.83 g/dL, white blood count was 100 x 109/L, and platelet count was 18 x 109/L.

On the basis of cytology and cytochemistry of bone mar- row aspiration ANLL with M2 FAB type was diagnosed. Im- munology typing revealed that the blast cells were CD33 and CD45 positive. The patient was treated with the IGCI-90 pro- tocol. Four months after diagnosis he is in complete remission.

Chromosome Studies The constitutional karyotype, from PHA-stimulated cultures of peripheral blood cells after the birth, was 4ZXY, + 21. At

From the Department of Pediatrics (E. B., E. O.), Medical Univer- sity of Debrecen, Hungary, and Pediatric Health Center (K. H.), Mis- kolc, Hungary.

Reprint requests to: Erzs~bet Balogh, M. B., C. Sc., Department of Pediatrics, Medical University of Debrecen, P.O. Box 32, H-4012 Debreeen, Hungary.

Received September 24, •993; accepted December 17, 1993.

the time of ANLL diagnosis cytogenetic analysis was carried out from 48-hour cultures of blood cells without mitogen stimulation. The karyotype of the leukemic cells was: 47,XY, t(8;21)(q22;q22), + 21c[12]. The chromosomes were stained using G-banding methods (Fig. 1).

DISCUSSION

There is a significant difference in the incidence of acquired chromosomal abnormalities of ANLL between patients with and without Down syndrome [2,3]. Cytogenetic studies of leukemic cells in Down patients show a hyperdiploid ten- dency; besides trisomy 21 there is no other specific cytogenetic abnormality. In our case the constitutional trisomy 21 was associated with acquired t(8;21)(q22;q22) in the M2 type of ANLL. The fact that chromosome 21 is in- volved in both constitutional and acquired chromosome aber- rations is interesting. In the translocation, chromosomal re- gion 21q22 is involved, which is responsible for the Down syndrome phenotype and is known as the chromosomal lo- cus of the c-ets 2 oncogene. Might this chromosomal region be responsible for the increased leukemic risk of Down syn- drome patients?

REFERENCES

1. Rochon M, Vaillancourt L, Robitaille D, Klinck WJ (1986): Cytogenetic pattern in leukemic cells of patients with constitu- tional chromosome anomalies. Cancer Genet Cytogenet 21: 365-368.

2. Alimena G, Billstr6m R, Casalone R, Gallo E, Mitelman F, Pasquali F (1985}: Cytogenetic pattern in leukemic cells of patients with constitutional chromosome anomalies. Cancer Genet Cytogenet 16:207-218.

3. Fong C, Brodeur GM (1987): Downs syndrome and leukemia: epidemiology, genetics, cytogenetics and mechanisms of leu- kemogenesis. Cancer Genet Cytogenet 28:55-76.

72 Cancer Genet Cytogenet 00 76:72-73 (1994) 0165-4608/94/$07.00

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F i g u r e 1 A representative G-banded karyotype from an unstimulated blood culture.