Patricia Martín-Jiménez

Chromosome 14q32 translocations involving the immunoglobulin heavy chain locus in chronic lymphocytic leukaemia identify a disease subset with poor prognosis

Immunophenotypic studies, fluorescence in situ hybridization (FISH) and conventional karyotyping were used to define the clinicobiological significance of 14q32 translocations involving the immunoglobulin gene locus (14q32/IGH) in 252 chronic lymphocytic leukaemia (CLL) patients. The following regions were studied: 13q14, centromere 12, 6q21; 11q22/ATM; 17p13/TP53, 14q32/IGH. Patients were classified as group 1 (favourable, i.e. 13q‐single or normal), group 2 (intermediate risk, i.e. +12, 6q‐, 1–2 anomalies), group 3 (unfavourable, i.e. 17p‐, 11q‐, complex karyotype), or group 4 (14q32/IGH translocation). Endpoints were treatment‐free survival (TFS) and overall survival (OS). One hundred and ten patients were included in group 1, 99 in group 2, 25 in group 3 and 18 in group 4. 14q32/IGH translocation partners were identified in eight cases (BCL2 in five cases, BCL11A, CCND3 and CDK6 in one case each). group 4 showed shorter TFS versus groups 2 and 1 (25% patients treated at 2 months vs. 12 (P = 0·02) and 20 months (P = 0·002), respectively) and shorter OS (25% patients dead at 18 months versus 50 (P = 0·0003) and >60 months (P < 0·0001) respectively. The 14q32/IGH translocation maintained prognostic significance at multivariate analysis on TFS (P = 0·025) and OS (P < 0·001), along with advanced stage and CD38+. These findings show that the 14q32/IGH translocation predicts for an unfavourable outcome in CLL and that this cytogenetic subset might be included as a separate entity in a hierarchical cytogenetic classification of CLL.

Functional class switch recombination may occur 'in vivo' in Waldenström macroglobulinaemia.

Waldenström macroglobulinaemia (WM) malignant cells have been considered incapable of undergoing class switch recombination (CSR). However, we report a WM patient who developed an IgG M‐component 4 years after diagnosis. When the second monoclonal component appeared, reverse transcription‐polymerase chain reaction showed the presence of pre (Cμ) and postswitch (Cγ) clonotypic isotypes; sequencing of these isotypes demonstrated that both corresponded to the single clone amplified at diagnosis, including the same complementarity‐determining region 3 and somatic mutation pattern. This proves that WM cells can undergo a functional in vivo CSR.

Clinical and prognostic value of discrepancies in microsatellite DNA regions between recipient and donor in human leukocyte antigen-identical allogeneic transplantation setting.

Background. Detection of recipient versus donor disparities in microsatellite DNA regions (short tandem repeats [STR]) allows for sensitive and specific monitorization of the degree of hematopoietic chimerism. It is well known that disparities between donor and recipient in various polymorphic systems (mainly human leukocyte antigen [HLA]) are associated with an increased incidence of graft-versus-host disease (GvHD). However, the possible biological role of STR discrepancies in GvHD development has not yet been well established. Methods. We evaluated 149 consecutive patients with hematologic malignancies receiving peripheral blood stem-cell transplantation from a human leukocyte antigen-identical sibling donor. A total of 15 STR regions were analyzed using the PowerPlex16 kit and classified as identical when recipient and donor share the same alleles, and mismatched when at least one of the alleles differed. Results. Higher severity of acute GvHD (II–IV, P=0.043) and shorter 5-year overall survival (P=0.016) was found in patients displaying more than 10 mismatches with respect to their donor. Additionally, higher risk of transplant-related mortality (P=0.019) was found in recipient–donor pairs with discrepancies in the D13S317 STR marker. Conclusion. The present data suggest that genetic incompatibilities outside the human leukocyte antigen region between donors and recipients influence the outcome of patients receiving stem-cell transplantation. In addition, disparities in the neighboring D13S317 region could influence transplant-related mortality.