Abstract
We here describe a novel unbalanced de novo translocation der(5)t(4;5)(q26;q21.1) in a 39-year-old male diagnosed with acute T-cell lymphoblastic leukemia. Bone marrow (BM) was massively infiltrated with 85 % highly proliferative polymorphic T-cell precursors. Immunologically, the malignant cells stained positive for CD7, CD34, intracytoplasmic CD3+, TdT + and negative for CD3 and CD5. G-banded chromosome analysis of BM cells showed the normal karyotype 46,XY[25] whereas BAC-based aCGH analysis revealed partial gain of 4q and partial loss of 5q. Multicolor karyotyping confirmed the presence of an unbalanced der(5)t(4;5) as the sole structural abnormality. Subsequent high-resolution oligonucleotide-based aCGH analysis showed that the der(5)t(4;5)(q26;q21.1) resulted in partial trisomy of 4q26qter (117,719,015-190,613,014) and partial monosomy of 5q21.1qter (100,425,442-180,857,866) and that there was no indication of any gene disruptions resulting from the breakages. Interphase FISH analysis using BAC-based specific probes for 4q26 and 5q21.1 confirmed the breakpoints and revealed approximately 80 % abnormal cells accordingly. At 4q26 the MIR1973 gene is located centromeric to the breakpoint in the copy number neutral region and the TRAM1L1 gene is located within the gained region. At 5q21.1 the genes ST8SIA4 and MIR548p are located centromeric to the breakpoint and no known genes up to approximately 1 Mb telomeric to the breakpoint in the copy number loss region. Interestingly, only the gene ST8SIA4 at 5q21.1 have been implicated in T-cell regulation as it encodes one of the key enzymes for polysialysation of surface proteins on dendritic cells which are important regulators for T-cell proliferation. The der(5)t(4;5) is thought to play a crucial role in the pathogenesis of acute T-ALL due to either gain of 4q, the loss of 5q, or deregulation of genes in proximity to the breakpoints.