Rabbit Anti-Human IKZF1 (a.a. 251-360) Polyclonal antibody

To investigate the prognosis of patients with adult B-cell acute lymphoblastic leukemia (B-ALL) with Ikaros family zincfinger 1 (IKZF1) mutation and determine the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in improving the clinical outcome, we detected the IKZF1 mutation and BCR-ABL fusion gene at diagnosis in the bone marrow of 164 adult patients with B-ALL, and analyzed the clinical data of these patients retrospectively. Our analysis showed that grade III-IV acute graft-versus-host disease and IKZF1 mutation in the transplantation group and age and IKZF1 mutation in the non-transplantation group were independent factors for poor prognosis by univariate and multivariate analyses. The 3-year overall survival (OS) and leukemia-free survival (LFS) rates were much lower in the IKZF1+/BCR-ABL+ subgroup than in the IKZF1+/BCR-ABL- and IKZF1-/BCR-ABL- subgroups in both the transplantation and non-transplantation groups. The 3-year OS and LFS rates were significantly higher in the transplantation group than in the non-transplantation group with IKZF1 mutation. The study demonstrated that IKZF1 mutation was an independent factor indicating the poor prognosis of adult B-ALL and much worse prognosis in the BCR-ABL+ subgroup in both non-transplantation and transplantation groups. However, allo-HSCT significantly improved the OS and LFS of patients and also their clinical outcomes.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic malignancy with few molecular alterations showing a consensual prognostic value. CRLF2 overexpression was recently identified in high-risk T-ALL patients. For these cases, no genomic abnormality was found to be associated with CRLF2 overexpression. IKZF1 has been recently shown to be a direct transcriptional regulator of CRLF2 expression. Moreover, it is known that NOTCH1 antagonizes IKZF1 in T-ALL. In light of these pieces of evidence, we reasoned that IKZF1 binding perturbation and CRLF2 upregulation could be associated in T-ALL. We evaluated two independent series of pediatric T-ALL cases (PHOP, n=57 and TARGET, n=264) for the presence of common T-ALL molecular abnormalities, such as NOTCH1/FBXW7 mutations. We also assessed CRLF2 and IKZF1 gene expression. CRLF2 overexpression was observed in 14% (PHOP) and 16% (TARGET) of T-ALL patients. No correlation was found between mRNA expression of CRLF2 and IKZF1 in both cohorts. Interestingly, we show that patients with mutations affecting NOTCH1-PEST domain and/or FBXW7 had higher CRLF2 expression (P=.04). In summary, we demonstrate for the first time that only mutations resulting in ICN1 (intracellular domain of NOTCH1) stabilization are associated with CRLF2 overexpression.