Stage specific over-expression of the dominant negative Ikaros 6 reveals distinct role of Ikaros throughout human B-cell differentiation

Genomic profiling of high-risk acute lymphoblastic leukemia

“…However, existing data have shown that expression of IK6 impairs B-lymphoid maturation 43,44 and pre-B-cell receptor signaling in Ph þ ALL cells. 45 Moreover, deletion of Ikzf1 accelerates leukemogenesis in a murine model of Ph þ ALL.…”

Genomic Characterization of Acute Leukemias

“…Furthermore, this technique has revealed that IKZF1, encoding for the transcription factor Ikaros and playing a pivotal role in lymphoid development [ 41 ], is frequently disrupted in ALL, particularly in BCR/ABL + cases, where it is deleted in both adult and pediatric cohorts in roughly 80% of cases, making it the most frequent aberration associated with BCR/ABL . The deletion of IKZF1 has functional consequences because it impairs B-lymphoid maturation and pre-B cell receptor signaling and accelerates leukemogenesis in a BCR/ABL + murine model [ 42 , 43 , 44 , 45 ]. Importantly, IKZF1 deletions are important predictors of a poor outcome in Ph+ ALL regardless of age, and they currently represent the hallmark of high-risk leukemias [ 46 , 47 , 48 , 49 ].…”

Cytogenetic and Molecular Predictors of Outcome in Acute Lymphocytic Leukemia: Recent Developments

“…The deletions either involve the entire IKZF1 locus, resulting in loss of function, or delete an internal subset of IKZF1 exons, resulting in the expression of dominant negative IKZF1 alleles. Expression of such dominant negative IKZF1 alleles in hematopoietic progenitors impairs lymphoid development [ 25 ], and loss of IKZF1 accelerates the onset of Ph+ ALL in a retroviral bone marrow transplant and transgenic models of this disease [ 26 ]. Several studies demonstrated that IKZF1 deletions are significantly associated with an increased relapse rate and adverse events and are correlated with poor outcome in patients with Ph+ ALL [ 27 – 29 ].…”