Reversal of -induced glucocorticoid resistance by dual targeting of AKT and ERK signaling pathways.

Although long-term survival in pediatric acute lymphoblastic leukemia (ALL) currently exceeds 90%, some subgroups, defined by specific genomic aberrations, respond poorly to treatment. We previously reported that leukemias harboring deletions or mutations affecting the B-cell transcription factor exhibit a tumor cell intrinsic resistance to glucocorticoids (GCs), one of the cornerstone drugs used in the treatment of ALL. Here, we identified increased activation of both AKT and ERK signaling pathways as drivers of GC resistance in deficient leukemic cells.

The many faces of IKZF1 in B-cell precursor acute lymphoblastic leukemia.

Transcription factor IKZF1 (IKAROS) acts as a critical regulator of lymphoid differentiation and is frequently deleted or mutated in B-cell precursor acute lymphoblastic leukemia. gene defects are associated with inferior treatment outcome in both childhood and adult B-cell precursor acute lymphoblastic leukemia and occur in more than 70% of -positive and -like cases of acute lymphoblastic leukemia. Over the past few years, much has been learned about the tumor suppressive function of IKZF1 during leukemia development and the molecular pathways that relate to its impact on treatment outcome.

Tracing the origins of relapse in acute myeloid leukaemia to stem cells.

In acute myeloid leukaemia, long-term survival is poor as most patients relapse despite achieving remission. Historically, the failure of therapy has been thought to be due to mutations that produce drug resistance, possibly arising as a consequence of the mutagenic properties of chemotherapy drugs. However, other lines of evidence have pointed to the pre-existence of drug-resistant cells.

Tumor suppressors BTG1 and IKZF1 cooperate during mouse leukemia development and increase relapse risk in B-cell precursor acute lymphoblastic leukemia patients.

Deletions and mutations affecting lymphoid transcription factor IKZF1 (IKAROS) are associated with an increased relapse risk and poor outcome in B-cell precursor acute lymphoblastic leukemia. However, additional genetic events may either enhance or negate the effects of deletions on prognosis. In a large discovery cohort of 533 childhood B-cell precursor acute lymphoblastic leukemia patients, we observed that single-copy losses of were significantly enriched in -deleted B-cell precursor acute lymphoblastic leukemia (=0.