Publication Date:
2015-12-03
Description:
Deregulated expression of the type I cytokine receptor, cytokine receptor-like factor 2 (CRLF2 -d), is observed in 5% of B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). It occurs via three known aberrations; a cryptic reciprocal translocation with the immunoglobulin heavy chain locus (IGH); an interstitial deletion within PAR1, resulting in the P2RY8-CRLF2 fusion; rare but recurrent CRLF2 mutation (F323C). All three result in overexpression of CRLF2, however alone it is insufficient to cause overt leukaemia. Mutations of the Janus kinase (JAK) family genes and the IL7 receptor, are recurrent (50% of CRLF2-d) and together with CRLF2 -d result in transformation of mouse BaF3 cells. We noted that outcome data from different study groups were inconsistent, with patients being classified as either high or intermediate risk. Thus, in this largest study to date, our aim was to acertain whether differences in clinical and/or genetic features between patients with CRLF2-d and involvement of either IGH or P2RY8 may define them as different disease entities and partly explain the outcome heterogeneity. Among 160 CRLF2-d patients, chromosomal analysis confirmed a high incidence of additional somatic copies of chromosomes X (39/88, 44%) and 21 (23/88, 26%) and identified that aneuploidy of chromosomes 9 (5/88, 6%) and 17 (7/88, 8%) were recurrent in both groups. From comparison of patients with IGH-CRLF2 and P2RY8-CRLF2, we noted a higher frequency of IKZF1 (79% v 37% p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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