IKZF1 deletions associate with CRLF2 overexpression leading to a poor prognosis in B-cell precursor acute lymphoblastic leukaemia

Abstract

Highlights CRLF2 overexpression associates with IKZF1 deletions that lead to a dominant-negative effect and with IKZF1 plus. Paediatric patients with a high load expression of IK4 isoform presented higher CRLF2 transcript levels. CRLF2 overexpression and IKZF1 deletions conferred poorer prognosis both to paediatric patients treated with RELLA05 protocol as well as to adult patients.

Pan-cancer analysis reveals the relationship between RCSD1 immune infiltration and clinical prognosis in human tumors

“…At the same time, we also screened the 100 genes with the strong correlation with RCSD1 in the GEPIA database, in which IKZF1 (r=0.87) and DOCK2 (r=0.87) were highly positively associated with RCSD1. Studies have shown that genetic mutations in IKZF1 are associated with poor prognosis in hematologic tumors and colorectal tumors ( 39 – 41 ); Low expression of DOCK2 is associated with a poor prognosis in colorectal cancer and lung cancer patients ( 42 – 44 ). Through GO and KEGG enrichment analysis, we can see that RCSD1-related genes are highly correlated with cellular immunomodulatory processes such as “T cell activation”, “lymphocyte differentiation”, and “mononuclear cell proliferation”.…”

Prognostic significance of copy number variation in B-cell acute lymphoblastic leukemia

“…Ribera reported that IKZF1 deletions were more prevalent in Ph+ B-ALL (52%) and correlated with advanced age and high white blood cell count ( 47 , 57 ). Another study reported that IKZF1 deletions correlated with the CALF2 gene overexpression ( P = 0.001), particularly in DN isoforms ( P = 0.006), regardless of age ( 54 ). Furthermore, IKZF1 deletions with CRLF2 overexpression indicated a poor prognosis in both adult and pediatric B-ALL patients ( 54 ).…”

“…Another study reported that IKZF1 deletions correlated with the CALF2 gene overexpression ( P = 0.001), particularly in DN isoforms ( P = 0.006), regardless of age ( 54 ). Furthermore, IKZF1 deletions with CRLF2 overexpression indicated a poor prognosis in both adult and pediatric B-ALL patients ( 54 ).…”

“…Some studies reported IKZF1 deletions in around 15% of pediatric B-ALL cases and 30%–40% of adult B-ALL cases ( 40 , 54 ). Perhaps, IKZF1 deletions in pediatric B-ALL are a hallmark of high-risk stratification and relapse independently carried by 70% of high-risk pediatric B-ALL ( 45 , 55 , 56 ).…”

Leucemia linfoblástica aguda do adulto: resultados da otimização da avaliação genética e dos protocolos terapêuticos

“…Maciel et al has just published a multicenter cohort from 6 centers, focusing their analysis on IKZF1 and CRLF2 genes in a mostly pediatric cohort (81). Interestingly, only 18% of patients with CRLF2 hyperexpression displayed translocation by FISH or F232C mutation in this gene, raising the question whether the assessment of CRLF2 expression would be enough for adults in terms of prognostic classification.…”