Complex karyotype in one patient with small cell variant of T-prolymphocytic leukemia. Analysis by G-banding and comparative genomic hybridization.

We report the genetic changes in a case of small cell variant of T-prolymphocytic leukemia. The use of comparative genomic hybridization allowed the characterization of otherwise hidden genetic abnormalities such as a high level amplification on 8q24, the chromosomal site of the c-MYC onco-gene, gain on 15q and deletions of 11p and 13q. The small cell variant of T-prolymphocytic leukemia (T-PLL) is a rare disorder representing around 20% of cases. 1 The case described here showed the clinical and immunologic features characteristic of T-PLL, including co-expression of CD4 and CD8, a phenotype frequent in the small cell variant of T-PLL. 1,2 While T-PLL is morphologically heterogeneous, the disease is characterized by recurrent chromosome abnormalities, chiefly inv(14) or t(14;14)(q11;q32) and trisomy 8q, thus supporting the hypothesis that all the morphologic T-PLL variants constitute a unique entity. 1-6 A 41-year old female was seen for evaluation of lymphocyto-sis. Physical examination revealed splenomegaly and lym-phadenopathy. Peripheral blood counts showed a white blood count of 104×10 9 /L with 91% small prolymphocytes, Hb 8.6 g/dL and platelets 131×10 9 /L. Bone marrow showed increased cellu-larity with a marked infiltration by small lymphocytes. Immu-nophenotyping in circulating lymphocytes demonstrated a CD3 + , CD7 + , CD38 + , CD4 + , CD8 + phenotype. A diagnosis of T-PLL was made (small cell variant), and the patient was treated with 3 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) with no response, but progression. The patient did not respond to fludarabine (1 cycle) and 2'-deoxycoformycin (2 injections), and died with widespread disease (organomegaly, rising counts, pleural effusion) six months after diagnosis. Kary-otype analysis at diagnosis failed. G-banding analysis post-treatment showed a complex hypodiploid karyotype with breakpoints at 14q and 7q: The following chromosomal imbalances were identified using comparative genomic hybridization (CGH): loss of chromosomal material on 4q11-q24, 4q32-q35, 6q24-q27, 7q36, 11p11-p12 and 13q13-q34; and gains on 8q24, 14q11-q32 and 15q23-q26 (Figure 1). A high amplification on 8q24 was detected. Chromosome translocations in T-PLL frequently involve the T-cell receptor (TCR) genes, with the TCRα/δ locus on chromosome 14q11 affected in 80% of cases. 1 In this disorder, rearrangements of 14q11 usually occur in association with tri-somy 8q, detected in the CGH analysis of our patient. Both similarities and discrepancies were found when conventional and CGH karyotypes were compared. CGH detected losses on chromosomes 6q and 7q that corresponded with the 6q and 7q deletions found in the …