Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The leukaemia-specific fusion oncoprotein RUNX1/RUNX1T1 (AML1/ETO), resulting from the chromosomal translocation (8;21) in acute myeloid leukaemia (AML), imposes a striking genotype-phenotype relationship upon this distinct subtype of AML, which is mediated by multiple, co-ordinate downstream effects induced by this chimeric transcription factor. We previously identified the LAT2 gene, encoding the adaptor molecule LAT2 (NTAL, LAB), which is phosphorylated by KIT and has a role in mast cell and B-cell activation, as a target of the repressor activity of RUNX1/RUNX1T1. These results were confirmed and extended by demonstrating downregulation of the LAT2 protein in response to conditional RUNX1/RUNX1T1 expression, and its absence in primary AML with the t(8;21). In contrast, in a cohort of 43 AML patients, higher levels of LAT2 were associated with myelomonocytic features. Differentiation of HL-60 and NB4 cells towards granulocytes by all trans-retinoic acid (ATRA) resulted in downregulation of LAT2; conversely, it was upregulated during phorbol ester-induced monocytic differentiation of HL-60 cells. Forced expression of LAT2 in Kasumi-1 cells resulted in a striking block of ATRA- and phorbol ester-induced differentiation, implicating disturbances of the graded expression of this adaptor molecule in the maturation block of myeloid leukaemia cells.
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PMID:Regulation of the adaptor molecule LAT2, an in vivo target gene of AML1/ETO (RUNX1/RUNX1T1), during myeloid differentiation. 2148 57

We evaluate the haematopathologic features of systemic mastocytosis associated with acute myeloid leukaemia (SM-AML) and the prognostic role of c-KIT mutation. Total 11 patients were enrolled. Cytochemistry using toluidine blue and tryptase was positive, as was immunohistochemistry for CD117 and CD25 on clustered mast cells; however, CD2 was expressed in only nine cases. In 10 cases, RUNX1-RUNX1T1 fusion gene was detected, and one patient presented with a t(5;6)(q22;q23) translocation at diagnosis. The c-KIT mutation D816V was detected in six patients. Patients with c-KIT mutations had higher relapse and death rates than those without; 4/5 (80.0%) and 5/6 (83.3%) vs. 1/5 (20%) and 2/5 (40%), respectively. Overall survival was also significantly shorter in cases with, than those without, c-KIT mutations. To identify rare cases of SM-AML, which have a dismal prognosis, c-KIT mutation study and careful examination for the presence of clustered mast cell infiltration by immunochemistry should be performed.
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PMID:The prognostic impact of c-KIT mutation in systemic mastocytosis associated with acute myeloid leukaemia patients. 2368 87