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Antigen receptor gene rearrangements reflect on the heterogeneity of adult Acute Lymphoblastic Leukaemia (ALL) with implications of cell-origin of ALL subgroups - a UKALLXII study

Lookup NU author(s): Professor Anthony Moorman

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Abstract

P>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 center dot 05). The heterogeneity in clinical outcome is suggested by the basic molecular processes of antigen receptor gene rearrangements as shown in this work.


Publication metadata

Author(s): Rai L, Casanova A, Moorman AV, Richards S, Buck G, Goldstone AH, Fielding AK, Foroni L

Publication type: Article

Publication status: Published

Journal: British Journal of Haematology

Year: 2010

Volume: 148

Issue: 3

Pages: 394-401

ISSN (print): 0007-1048

ISSN (electronic): 1365-2141

Publisher: Wiley-Blackwell Publishing Ltd.

URL: http://dx.doi.org/10.1111/j.1365-2141.2009.07966.x

DOI: 10.1111/j.1365-2141.2009.07966.x


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