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Down Syndrome, Acute Lymphoblastic Leukemia, and t(8;14)(q11;q32)

It is unclear why chi ldren with Down syndrome (DS) have a 10- to 20-fold increased risk of developing acute leuke- mias. The acute lymphoblas t ic leukemia (ALL) in DS has not been noted to be different from ALL developed from normal ind iv idua ls in terms of morphology, immunophe- notypes, or cytogenetics. Secker-Walker et al. repor ted two DS pat ients wi th acquired t(8;14)(q11;q32) in ALL [1]. We report a th i rd case of DS who deve loped ALL and a s imilar cytogenetic abnormality.

A 4-year-old boy with DS presented with pallor, pete- chiae, and hepatosplenomegaly. The full b lood counts showed hemoglobin 8.0 g/dL, white cell count 30.2 x 109/L with 85% blasts, and a platelet count 12 × 109/L. Bone marrow examinat ion confirmed the diagnosis of ALL with FAB L1 morphology. Immunopheno type of the blasts showed a common ALL phenotype. Cytogenetic s tudy re- vealed 47,XY, t(8;14)(q11;q32),+21. Remission was achieved according to the United Kingdom ALL XI protocol of the Medical Research Council and had been main ta ined for 4 months since then.

Translocation (8;14)(q11;q32) is a rare finding in leuke- mia cytogenetics, account ing for no more than 1% in major series [2]. Ten cases have been descr ibed in the liter- ature [1-5]. There seems to be an excess of the male gen- der (nine cases) and a young age (seven cases under the age of 16 years). Most pat ients have B-lineage ALL, expressing CD10. There were two cases of nul l ALL [3, 4]. Two patients had addi t ional chromosomal t ranslocat ion involving t(9;22)(q34;q11).

Including the present case, three (27%) of the 11 pat ients have DS [1]. Their c l inical characterist ics are summar ized in Table 1. None has addi t ional chromosomal translocations. As patients wi th DS consti tute only a minor i ty of ALL (< 2%), the associat ion between the chro- mosomal t ranslocat ion (8;14)(q11;q32) and DS with ALL is striking.

Further s tudies on the molecular events, which may involve the immunoglobu l in H gene on 14q32 and the IL7 locus on 8 q l l (which is involved in the control of lym- phopoiesis) , may provide a hint to the pathogenesis of ALL in DS.

ANSELM C. W. LEE Department of Pediatrics L. C. CHAN Tuen Mull Hospital, New Territories

Hong Kong; K. W. KWONG Department of Hematology

The University of Hong Kong Queen Mary Hospital, Hong Kong.

We thank Miss L. M. Ching for cytogenetic analysis.

REFERENCES

1. Secker-Walker LM, Hawkins )M, Prentice HG, Mackie PH, Heerema NA, Provisor AJ (1993): Two Down syndrome patients with an acquired transiocation, t(8;14)(qll;q32), in early B-lineage acute lymphoblastic leukemia. Cancer Genet Cytogenet 70:148-150.

2. Carroll AJ, Raimondi SC, Borowitz MJ, Amylon MD, Rivera G, Pullen DJ, Crist WM (1988): A new nonrandom 8;14 transloca- tion in children with acute lymphoblastic leukemia (abstract). Am J Hum Genet 43a:21.

3. Kardon NB, Slepowitz G, Kochen JA (1982): Childhood acute lymphoblastic leukemia associated with an unusual 8;14 translocation. Cancer Genet Cytogenet 6:339-343.

4. Wodzinski MA, Watmore AE, Lilleyman JS, Potter AM (1991): Chromosomes in childhood acute lymphoblastic leukaemia: karyotypic patterns in disease subtypes. J Clin Pathol 44:48- 51.

5. Testoni N, Zaccaria A, Martinelli G, Pelliconi S, Buzzi M, Farabegoli P, Panzica G, Tura S (1993): t(8;14)(q11;q32) in acute lymphoid leukemia: description of two cases. Cancer Genet Cytogenet 67:55-58.

Table I Clinical features of t(8;14)(q11;q32)-associated ALL in Down syndrome

Case Sex/age WBC x 1 0 9 / L Immunophenotype Outcome

1 M/3 34 Common Alive in remission 6+ years 2 M/32 1.9 Common Died in remission 8 months 3 M/4 30.2 Common Alive in remission 5 + months

Abbreviation: WBC, whi te b lood cell count at presentat ion.

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