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.
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.
Rai
Lena
L
Haematology Department, Royal Free Hospital, Pond Street, London, NW3 2QG, UK. l.rai@medsch.ucl.ac.uk
Casanova
Anouska
A
Moorman
Anthony V
AV
Richards
Sue
S
Buck
Georgina
G
Goldstone
Anthony H
AH
Fielding
Adele K
AK
Foroni
Letizia
L
D000293:Adolescent; D000328:Adult; D022801:Complementarity Determining Regions / Q000235:genetics; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D011379:Prognosis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D014178:Translocation, Genetic; D055815:Young Adult
D022801:Complementarity Determining Regions; D007135:Immunoglobulin Variable Region; D011948:Receptors, Antigen, T-Cell