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Cytogenetic and molecular investigations of Acute Lymphoblastic Leukaemia (ALL) have identified the existence of distinct clinical subgroups. Molecular monitoring of clonal Immunoglobulin and T cell receptor (IG/TR) gene rearrangements has become an important tool in stratification of therapy of ALL. In order to determine whether certain features of the patient-specific rearrangements could hold further prognostic clues or provide information on the cell of origin of ALL, a comprehensive analysis of structural and biological features (V gene usage, coding frame and mutational status and complementarity-determining region -III length) of 473 IG/TR rearrangements identified in 229 adults with ALL was carried out. Distinct variable-gene usage profiles were identified between ALL subgroups, particularly for patients positive for BCR-ABL1 compared to MLL-AFF1 positive leukaemias; suggesting that the former is derived from a more mature B progenitor. Interestingly, occurrence of TRGV1-TRGV8 was prognostic for better event-free survival (31% at 4 years with vs. 0% at 4 years without, P = 0.05). The heterogeneity in clinical outcome is suggested by the basic molecular processes of antigen receptor gene rearrangements as shown in this work.

Original publication

DOI

10.1111/j.1365-2141.2009.07966.x

Type

Journal article

Journal

Br J Haematol

Publication Date

02/2010

Volume

148

Pages

394 - 401

Keywords

Adolescent, Adult, Complementarity Determining Regions, Female, Gene Rearrangement, T-Lymphocyte, Humans, Immunoglobulin Variable Region, Immunophenotyping, Male, Middle Aged, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, Receptors, Antigen, T-Cell, Translocation, Genetic, Young Adult