The AML1/ETO target gene LAT2 interferes with differentiation of normal hematopoietic precursor cells

Abstract

The adaptor protein linker activator of T-cells 2 (LAT2) is a known AML1/ETO target gene whose function during normal hematopoiesis is unknown. We addressed the role of LAT2 during erythroid and myeloid differentiation of normal human CD34+ hematopoietic cells. LAT2 is expressed at low levels in CD34+ cells and upregulated during cytokine-induced myeloid and erythroid differentiation. Forced LAT2 expression leads to a delay of erythroid and myeloid differentiation keeping CD34+ cells in a more immature state, whereas LAT2 knockdown accelerates differentiation. It is tempting to speculate that by affecting the differentiation capacity of normal hematopoietic progenitors, LAT2 may contribute to the pathogenesis of AML.

NTAL is associated with treatment outcome, cell proliferation and differentiation in acute promyelocytic leukemia

“…NTAL protein levels are significantly decreased in a time-dependent manner in NB4 cells (an acute promyelocytic leukemia [APL] cell line) treated with all-trans retinoic acid (ATRA). Similarly, decreased NTAL expression has also been observed in other AML cell lines treated with drugs that induce differentiation 9,10 . In APL, NTAL depletion from lipid rafts in response to arsenic trioxide (ATO) decreases cell viability through regulation of the Akt/PI3K pathway 11 .…”

“…NTAL is reported to be expressed in acute myeloid leukemia (AML) cells, but its expression varies significantly among the different subtypes of AML 9 . NTAL expression in primary AML blasts has already been found to be associated with myelomonocytic features 10 .…”

Runx1t1 promotes the neuronal differentiation in rat hippocampus

“…The significant expression and the general clues provided by the protein sequence and structure suggested that Runx1t1 might act as a regulator to modulate development of the nervous system. Several studies have suggested that Runx1t1 was involved in the proliferation and affected the differentiation capacity of the hematopoietic progenitors [18,[27][28][29]. Despite extensive efforts to understand the function of Runx1t1 protein in the etiology of cancer, the lack of knowledge about their function in normal embryonic development continues to persist.…”

Impedimetric quantification of the formation process and the chemosensitivity of cancer cell colonies suspended in 3D environment

“…Therefore, if there are selfrenewing stem cells among cancer cells, the sphere culture system might be able to isolate cancer stem cells from a pool of cancer cells. Hence, investigations of the formation process and the chemosensitivity of cancer cell colonies are crucial in cancer research (Liu et al, 2012;Lee et al, 2014;Essig et al, 2014). The colony formation assay became a gold standard for measuring the development of early tumors and the effects of cytotoxic agents on tumors in vitro.…”

“…However, conventional bio-assays quantifying indicative cellular components are ineffective especially for large cancer cell colonies. Currently, quantification of cancer cell colonies is achieved by manual counting under microscope (Liu et al, 2012;Lee et al, 2014;Essig et al, 2014;Jin et al, 2013). Because cell colonies are suspended in 3D hydrogel and present irregular shapes, this is challenging to microscopically quantify the colony number and size without subjective bias.…”