Among 18 BCR-ABL+ leukemias presenting acquired trisomy of chromosome 21, we report a high frequency (33%) of recurrent point mutations (4 in myeloid blast crisis [BC] CML and one in chronic phase CML) within the DNA-binding region of RUNX1.
The increased expression of p21/WAF/Cip1 in primary leukemic blasts suggests that elevated p21/WAF/Cip1 levels may contribute to specific features observed in AML1-ETO positive leukemia.
Combined high-resolution array-based comparative genomic hybridization and expression profiling of ETV6/RUNX1-positive acute lymphoblastic leukemias reveal a high incidence of cryptic Xq duplications and identify several putative target genes within the commonly gained region.
We compared the leukemia cell gene expression profiles of 16 TEL/AML1-positive ALL patients to those of 44 TEL/AML1-negative patients, whose blast cells did not contain any additional recurrent translocation.
The TEL-AML1 transgenic zebrafish models human pre-B ALL, identifies the molecular pathways associated with leukemia development, and serves as the foundation for subsequent genetic screens to identify modifiers and leukemia therapeutic targets.
Thus, our data indicate that physical interaction and synergy between GATA1 and RUNX1 are retained in DS-AMKL, although it is still possible that increased RUNX1 activity plays a role in the development of leukemia in DS.
The combined overexpression of RUNX1 and NCAM during stress hematopoiesis in children with DS might be a key factor in the development of overt leukemia and/or in the growth advantage of the malignant GATA1s clone in ML- DS.
The fusion gene produces a chimeric transcription factor that suppresses the expression of AML1-target genes via the MTG8 part of the chimeric protein, which is thought to be the primary cause of leukemia.
This is consistent with the hypothesis that a second mutation has to occur, either in RUNX1 or another gene, to cause leukemia among individuals harboring RUNX1 FPD/AML mutations and that the propensity to acquire these additional mutations is determined, at least partially, by the initial RUNX1 mutation.