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.
IKZF1rs4132601 and rs10272724 could be considered significant risk contributors to childhood acute lymphoblastic leukaemia and may impact the iron profiles in these children.
Common CNAs involved CDKN2A/2B (30.3%), IKZF1 (27.3%), PAX5 (9.1%), RB1 (9.1%), BTG1 (6.7%), and ETV6 (6.7%), which regulate cell cycle, B lymphopoiesis, or act as tumor suppressors in ALL.
We demonstrated the association of IKZF1 polymorphism rs4132601 T/G with increased risk of ALL among Tunisian pediatric cohort, with altered phenotypic changes among ALL patients.
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.
The multiplex ligation-dependent probe amplification (MLPA) method was used to detect the copy number alterations (CNAs) of IKAROS family zinc finger 1 (<i>IKZF1</i>), paired box 5 (<i>PAX5</i>), ETS variant 6 (<i>ETV6</i>), RB transcriptional corepressor 1 (<i>RB1</i>), BTG anti-proliferation factor 1 (<i>BTG1</i>), early B-cell factor 1 (<i>EBF1</i>), cyclin dependent kinase inhibitor 2A/2B (<i>CDKN2A/2B</i>) and cytokine receptor like factor 2 (<i>CRLF2</i>) genes in 87 adults with acute lymphoblastic leukemia (ALL) in China.
By contrast, the MRD15 was higher in Ikaros family Zinc Finger Protein 1 (<i>IKZF1)</i>-deleted BCP-ALL patients than in BCP-ALL patients without <i>IKZF1</i> deletions [1.18% (0.06-12.0%) vs 0.33% (0.03-2.6%); p=0.003].
Patients and Methods The analysis involved 991 patients with BCP ALL treated in the Associazione Italiana Ematologia ed Oncologia Pediatrica-Berlin-Frankfurt-Muenster (AIEOP-BFM) ALL 2000 trial with complete information for copy number alterations of IKZF1, PAX5, ETV6, RB1, BTG1, EBF1, CDKN2A, CDKN2B, Xp22.33/Yp11.31 (PAR1 region; CRLF2, CSF2RA, and IL3RA), and ERG; replication of findings involved 417 patients from the same trial.
Intensifying Treatment of Childhood B-Lymphoblastic Leukemia With IKZF1 Deletion Reduces Relapse and Improves Overall Survival: Results of Malaysia-Singapore ALL 2010 Study.
In this issue of Cancer Cell, Churchman et al. add to the list of leukemia predisposition genes with the identification and characterization of germline IKZF1 variants in childhood ALL.
These results identify IKZF1 as a leukemia predisposition gene, and emphasize the importance of germline genetic variation in the development of both familial and sporadic ALL.
The IKZF1 SNPs, rs10235796 and rs6964969, and the CDKN2A SNP rs3731246 (previously unreported) could serve as risk markers for ALL susceptibility in Yemeni children.
Tumor suppressors BTG1 and IKZF1 cooperate during mouse leukemia development and increase relapse risk in B-cell precursor acute lymphoblastic leukemia patients.
Recent experimental mouse modeling of B-progenitor ALL has shown that IKZF1 alterations have multiple effects, including arresting differentiation, skewing lineage of leukemia from myeloid to lymphoid, and, in Ph+ leukemia, conferring resistance to tyrosine kinase inhibitor (TKI) therapy without abrogating ABL1 inhibition.