Transformation by oncogenic mutants and ligand-dependent activation of FLT3 wild-type requires the tyrosine residues 589 and 591.

Purpose: Mutations in the receptor tyrosine kinase FLT3 are found in up to 30% of acute myelogenous leukemia patients and are associated with an inferior prognosis. In this study, we characterized critical tyrosine residues responsible for the transforming potential of active FLT3-receptor mutants and ligand-dependent activation of FLT3-WT.

Experimental Design: We performed a detailed structure-function analysis of putative autophosphorylation tyrosine residues in the FLT3-D835Y tyrosine kinase domain (TKD) mutant.

Overexpression of CDX2 perturbs HOX gene expression in murine progenitors depending on its N-terminal domain and is closely correlated with deregulated HOX gene expression in human acute myeloid leukemia.

The mechanisms underlying deregulation of HOX gene expression in AML are poorly understood. The ParaHox gene CDX2 was shown to act as positive upstream regulator of several HOX genes. In this study, constitutive expression of Cdx2 caused perturbation of leukemogenic Hox genes such as Hoxa10 and Hoxb8 in murine hematopoietic progenitors.

Global patterns in human mitochondrial DNA and Y-chromosome variation caused by spatial instability of the local cultural processes.

Because of the widespread phenomenon of patrilocality, it is hypothesized that Y-chromosome variants tend to be more localized geographically than those of mitochondrial DNA (mtDNA). Empirical evidence confirmatory to this hypothesis was subsequently provided among certain patrilocal and matrilocal groups of Thailand, which conforms to the isolation by distance mode of gene diffusion. However, we expect intuitively that the patterns of genetic variability may not be consistent with the above hypothesis among populations with different social norms governing the institution of marriage, particularly among those that adhere to strict endogamy rules.