Prognostic impact of IKZF1 deletion in adults with common B-cell acute lymphoblastic leukemia

Abstract

Background: Interrogate the impact of IKZF1 deletion on therapy-outcomes of adults with common B-cell acute lymphoblastic leukemia. Methods: One hundred sixty-five consecutive adults with common B-cell ALL were tested for IKZF1 deletion and for BCR/ABL. Deletions in IKZF1 were detected using multiplex RQ-PCR, multiplex fluorescent PCR, sequence analysis and multiplex ligation-dependent probe amplification (MLPA). BCR/ABL was detected using RQ-PCR. All subjects received chemotherapy and some also received an allotransplant and tyrosine kinase-inhibitors. Multivariate analyses were done to identify associations between IKZF1 deletion and other variables on non-relapse mortality (NRM), cumulative incidence of relapse (CIR), leukemia-free survival (LFS) and survival. The adverse impact of IKZF1 deletion on outcomes was stronger in subjects without vs. with BCR-ABL1 and in subjects receiving chemotherapy-only vs. an allotransplant. Conclusions: IKZF1 deletion was independently-associated with a higher relapse risk and worse LFS and survival in adults with common B-cell ALL after adjusting for other prognostic variables and differences in therapies. These data suggest IKZF1 deletion may be a useful prognostic variable in adults with common B-cell ALL, especially in persons without BCR-ABL1 and those receiving chemotherapy-only. Transplants appear to overcome the adverse impact of IKZF1 deletion on therapy-outcomes but confirmation in a randomized study is needed.

S100A16suppresses the growth and survival of leukaemia cells and correlates with relapse and relapse free survival in adults with Philadelphia chromosome‐negative B‐cell acute lymphoblastic leukaemia

“…BCR‐ABL1 transcripts and KMT2A rearrangements were detected with quantitative real‐time polymerase chain reaction (RT‐qPCR) (Beillard et al , ; Qin et al , ). IKZF1 deletions were detected as described previously (Yao et al , ).…”

“…BCR-ABL1 transcripts and KMT2A rearrangements were detected with quantitative realtime polymerase chain reaction (RT-qPCR) (Beillard et al, 2003;Qin et al, 2008). IKZF1 deletions were detected as described previously (Yao et al, 2016). in Iscove's modified Dulbecco's medium (IMDM) (Gibco, Billings, MT, USA) containing 10% fetal bovine serum (FBS) (Gibco) and 1% penicillin-streptomycin liquid (Solarbio, Beijing, China).…”

The Clinical Significance and Biological Function ofDPEP1in B-cell Acute Lymphoblastic Leukemia

“…BCRABL1 transcripts and KMT2A (MLL) rearrangements were detected with quantitative real-time polymerase chain reaction (RT-qPCR) 17,18 . IKZF1 deletion was detected as described 10 . Risk cohort was defined as previously described 11 .…”

t(1;7)(p36;p12) IKZF1/PRDM16

“…2017;21(6) hematopoietic stem and progenitor cells) that regulate the expression of a number of hematopoietic genes and whose high expression in acute myeloid leukemia is associated with poor prognosis (Unnikrishnan et al, 2016). IKZF1 deletions are associated with unfavorable prognosis in childhood B-cell precursor acute lymphoblastic leukemia (ALL) (Boer et al, 2016), and is associated with a higher relapse risk and worse survival in adults with common B-cell ALL (Yao et al, 2016). IKZF1 mutations were found in cases of common variable immunodeficiency syndrome with progressive B lymphopenia and an increased risk of acute lymphoblastic leukemia (Kuehn et al, 2016).…”