Therefore, we sought to determine whether molecular abnormalities involving the Ikaros gene could contribute to the development of acute lymphoblastic leukemia (ALL) in infants.
In addition, IKZF1 has been implicated in roles involved in some hematologic traits or abnormalities, such as erythrocyte measures, myelofibrosis, and acute lymphoblastic leukemia (ALL), which may be common clinical manifestations or co-occurrence hematological diseases of patients with SLE.
We identified CRLF2 overexpression as an intermediate-risk marker and Ik6 variant of IKZF1 gene as a high-risk one when stratifying pediatric B-ALL cases according to cytogenetic/molecular risks.
Our results demonstrate that the IKAROS promotes PHF2 expression, and suggest that PHF2 <sup>low</sup> expression works with the IKAROS gene deletion to drive oncogenesis of ALL.
A subset of B-ALL patients with IKZF1 alterations have a transcriptional profile similar to BCR-ABL1-positive ALL, and these patients commonly have novel rearrangements and mutations resulting in aberrant cytokine receptor signaling and activation of kinase signaling cascades, including rearrangement of CRLF2 and activating mutations of Janus kinases (JAK1 and JAK2).
As controversy exists regarding the prognostic significance of genomic rearrangements of CRLF2 in pediatric B-precursor acute lymphoblastic leukemia (ALL) classified as standard/intermediate-risk (SR) or high-risk (HR), we assessed the prognostic significance of CRLF2 mRNA expression, CRLF2 genomic lesions (IGH@-CRLF2, P2RY8-CRLF2, CRLF2 F232C), deletion/mutation in genes frequently associated with high CRLF2 expression (IKZF1, JAK, IL7R), and minimal residual disease (MRD) in 1061 pediatric ALL patients (499 HR and 562 SR) on COG Trials P9905/P9906.
We assessed the status of BCR-ABL1 and IKZF1 genes in 2 pairs of monozygotic twins, one pair concordant, the other discordant for Philadelphia chromosome positive (Ph(+)) ALL.
We performed a comprehensive analysis of the impact of IKZF1(del) in a large cohort of children (n=1223) with BCR-ABL1-negative BCP-ALL treated in the EORTC-CLG trial 58951.
An 11-year-old male patient with the deletion of <i>IKZF1</i> (Ikaros family zinc finger 1) and positive Breakpoint Cluster Region-C-Abelson oncogene 1(<i>BCR-ABL1</i>) acute lymphoblastic leukemia developed mucositis, gastrointestinal toxicity, hepatotoxicity, myelosuppression, and severe dermatologic toxicity during the first and second courses of high-dose methotrexate.
The IKZF1 SNPs, rs10235796 and rs6964969, and the CDKN2A SNP rs3731246 (previously unreported) could serve as risk markers for ALL susceptibility in Yemeni children.
One recently identified subtype of pediatric B-precursor acute lymphoblastic leukemia (ALL) has been termed BCR-ABL1-like or Ph-like because of similarity of the gene expression profile to BCR-ABL1 positive ALL suggesting the presence of lesions activating tyrosine kinases, frequent alteration of IKZF1, and poor outcome.
The genomic profile of ETV6-ABL1 acute lymphoblastic leukemia resembled that of BCR-ABL1 and BCR-ABL1-like cases with 80% of patients having concurrent CDKN2A/B and IKZF1 deletions.