IKZF2 mutation

Jude protocol for outpatient delivery, including once weekly daunorubicin and vincristine in initial therapy, postponing intrathecal chemotherapy until day 22, prophylactic oral antibiotics/ anti-mycotics, use of generic drugs, and no central nervous system radiation. Outcomes were comparable to those reported in the control arm of the Total Therapy XI study but inferior to current treatment protocols in high-income countries. Using an outpatient- based modification of the St. Jude Total XI protocol, we obtained good results with relatively few hospitalizations or adverse events and substantial savings.

Treatment of B-ALL cells with a specific CK2 inhibitors, CX-4945, resulted in increased Ikaros binding at the RAB21 promoter and reduced RAB21 expression...Together, these data demonstrate that Ikaros and CK2 regulate transcription and overall expression of RAB21 in B-cell ALL. Results uncovered an interplay between CK2 and Rab GTPase signaling pathways and suggest a mechanism by which CK2 regulates Rab21 activity in leukemia.

The human immunophenotype was recapitulated in a murine model carrying the corresponding human mutation. As demonstrated here, AIOLOS plays a key role in T and B cell development in humans, and the particular gene variant described is strongly associated with immunodeficiency and likely malignancy.

Immune checkpoint inhibitors (ICIs) including atezolizumab, pembrolizumab have shown durable responses and have been approved by FDA. This study shows that ZNF479 mutation may serve as a potential positive biomarker of ICIs in lung cancer since it correlated with higher TMB, up regulation of M1 macrophages, CD8 T cells and down regulation of Myeloid dendritic cells.

Mechanistically, the mutant was fully penetrant and had a dominant negative effect over AIOLOS wildtype function. Our findings demonstrate that AIOLOS plays a key role in T and B cell development in humans and also associates abnormal AIOLOS function with CID, PJP and potential development of CLL.