Disease relevance of Myst4

• Mice homozygous for the querkopf mutation have craniofacial abnormalities, fail to thrive in the postnatal period and have defects in central nervous system development [1].
• MY3 and MY4 are expressed by normal monocytes and by greater than 90% of patients with acute monocytic leukemia or acute myelomonocytic leukemia, but are detected much less often on other types of myeloid leukemia [2].
• In contrast, expression of constitutively activated H-Ras in bone-marrow cells resulted in the in vitro growth, in the absence of exogenous factors, of colonies that contained only macrophages and of lines of cells resembling dendritic cells, and, upon in vivo injection of the transduced cells, a fatal histiocytosis/monocytic leukemia [3].
• Expression of a constitutively active mutant of M-Ras in normal bone marrow is sufficient for induction of a malignant mastocytosis/mast cell leukemia, distinct from the histiocytosis/monocytic leukemia induced by expression of activated H-Ras [3].
• M206 also reacted intensely with the immature leukemic cells from patients with acute monocytic leukemia but was unreactive with other types of leukemic cells except cells from chronic myelogenous leukemia which showed varied patterns of reactivities [4].

High impact information on Myst4

• Furthermore, the selective depletion of the population of this stem cell in querkopf mutant mice (which are deficient in production of olfactory neurons) suggests that it acts as a major functional stem cell in vivo [5].
• Furthermore, the mixed populations of cells in culture and in the tumors phenotypically resembled the leukemic cells from patients with monocytic leukemia with histiocytic differentiation (acute myeloid leukemia-M5c), a newly proposed subtype of myeloid leukemia [6].
• Querkopf, a MYST family histone acetyltransferase, is required for normal cerebral cortex development [1].
• Our results suggest that Querkopf is an essential component of a genetic cascade regulating cell differentiation in the cortex, probably acting in a multiprotein complex regulating chromatin structure during transcription [1].
• We purified from activated T lymphocytes a novel, highly conserved, 116-kDa, intracellular protein that occurred at high levels in the large, dividing cells of the thymus, was up-regulated when resting T or B lymphocytes or hemopoietic progenitors were activated, and was down-regulated when a monocytic leukemia, M1, was induced to differentiate [7].

Biological context of Myst4

• At all stages of fetal development querkopf mutant mice show a reduced number of cells in the cortical plate resulting in a reduction in the size of the adult cortex [8].
• THP-1 cells are a monocyte-like cell line derived from a patient with acute monocytic leukemia and unlike other leukemic cell lines has a normal diploid karyotype [9].

Anatomical context of Myst4

• Querkopf shows a dynamic pattern of expression in the telencephalon [8].
• Selective compounds were active against the growth of Tmolt(3) and Tmolt(4) leukemias and THP-1 acute monocytic leukemia, liver Hepe-2, ovary 1-A9, ileum HCT-8 adenocarcinoma, and osteosarcoma HSO [10].

Associations of Myst4 with chemical compounds

• Although 2'-deoxycoformycin (dCF) has been reported in clinical trials to be less effective against myeloid than lymphoid malignancies, it may be useful for treating monocytic leukemia with the aid of 2'-deoxyadenosine (dAd) analogs [11].
• Male and female rats treated with dimethoate developed monocytic leukemia [12].
• Vidarabine and 2-deoxycoformycin as antileukemic agents against monocytic leukemia [11].

Other interactions of Myst4

• It was shown by in situ hybridization that all the component cells were positive for myeloperoxidase mRNA in granulocytic leukemia, whereas only half the cells were positive in myelomonocytic leukemia and none in monocytic leukemia [13].

References