ABSTRACT
Recently, we and others described a new chromosomal rearrangement, that is, inv(7)(p15q34) and t(7;7)(p15;q34) involving the T-cell receptor beta (TCRbeta) (7q34) and the HOXA gene locus (7p15) in 5% of T-cell acute lymphoblastic leukemia (T-ALL) patients leading to transcriptional activation of especially HOXA10. To further address the clinical, immunophenotypical and molecular genetic findings of this chromosomal aberration, we studied 330 additional T-ALLs. This revealed TCRbeta-HOXA rearrangements in five additional patients, which brings the total to 14 cases in 424 patients (3.3%). Real-time quantitative PCR analysis for HOXA10 gene expression was performed in 170 T-ALL patients and detected HOXA10 overexpression in 25.2% of cases including all the cases with a TCRbeta-HOXA rearrangement (8.2%). In contrast, expression of the short HOXA10 transcript, HOXA10b, was almost exclusively found in the TCRbeta-HOXA rearranged cases, suggesting a specific role for the HOXA10b short transcript in TCRbeta-HOXA-mediated oncogenesis. Other molecular and/or cytogenetic aberrations frequently found in subtypes of T-ALL (SIL-TAL1, CALM-AF10, HOX11, HOX11L2) were not detected in the TCRbeta-HOXA rearranged cases except for deletion 9p21 and NOTCH1 activating mutations, which were present in 64 and 67%, respectively. In conclusion, this study defines TCRbeta-HOXA rearranged T-ALLs as a distinct cytogenetic subgroup by clinical, immunophenotypical and molecular genetic characteristics.
Subject(s)
Homeodomain Proteins/genetics , Leukemia-Lymphoma, Adult T-Cell/genetics , Receptors, Antigen, T-Cell, alpha-beta/genetics , Adolescent , Adult , Child , Chromosome Deletion , Chromosome Inversion , Female , Gene Rearrangement, T-Lymphocyte , Homeobox A10 Proteins , Humans , Immunophenotyping , Leukemia-Lymphoma, Adult T-Cell/pathology , Leukemia-Lymphoma, Adult T-Cell/physiopathology , Male , Middle Aged , Receptor, Notch1/genetics , Transcriptional Activation , Translocation, GeneticABSTRACT
The development of secondary leukemia in donor cells after allogeneic stem cell transplantation is a rare event. We describe the occurrence of acute myeloid leukemia in donor cells 4 years after a stem cell transplantation for multiple myeloma. The multiple myeloma was relapsing at the time of the onset of acute myeloid leukemia. Secondary leukemia in donor cells after transplantation for multiple myeloma has not yet been reported.
