Disease relevance of GPM6A

• We evaluated 48 archival cases of acute erythroleukemia and divided them into 3 groups: M6a, corresponding to the traditional French-American-British M6 category; M6b, which is pure erythroleukemia; and M6c, in which myeloblasts and pronormoblasts each account for more than 30% of cells by the French-American-British exclusion criteria [1].
• Patients with this type of leukemia traditionally have been treated with a standard myeloid protocol, with a wide variation in prognosis between M6a, which has a similar prognosis to acute myelogenous leukemias, and M6b, with an extremely poor outcome despite aggressive therapy [2].
• RESULTS: Fifty-three patients met the criteria of M6a subtype of the WHO classification, and 2 were classified as having pure erythremia (M6b); 7 cases could not be classified according to the WHO criteria [3].

High impact information on GPM6A

• The genes for membrane glycoprotein (M6a) and chloride channel 3 (CLCN3) were analyzed by direct sequencing for mutations [4].
• To date, three different gene products, DMalpha/DM-20/PLP, DMbeta/M6a, and DMgamma/M6b, have been isolated from certain primitive fish species, mouse, and human central nervous system (CNS) [5].
• M6a appeared in post-mitotic neurons of the brain and spinal cord as early as E10, and later in the hippocampus, cerebral cortex, and the granule cells of the cerebellum [6].
• These results support the idea that M6a implicates in neuronal differentiation as a novel Ca(2+) channel gated selectively by phosphorylation with PKC in the downstream of NGF signaling pathway [7].
• Calculating the proerythroblasts as a component of total bone marrow erythroids provides a complimentary method for delineating the pure red cell erythroleukemia (M6B) and mixed variant (M6C), similar to that for the myeloid/erythroid (M6A) leukemia [8].

Biological context of GPM6A

• The human gene (GPM6A) contains an open reading frame of 834 nucleotides encoding a peptide of 278 amino acids [9].
• We assigned the GPM6A locus to chromosome bands 4q33-->q34 by radiation hybrid mapping [9].

Anatomical context of GPM6A

• Compared to M6A, both the M6B (P< 0.0001) and M6C (P< 0.0001) variants showed a statistically significant increase in the percentage of bone marrow erythroid cells, proerythroblasts, and the proerythroblasts/erythroid ratios [8].

Associations of GPM6A with chemical compounds

• Isolation and mapping of the human glycoprotein M6 gene (GPM6A) to 4q33-->q34 [9].
• The minor metabolites were identified, by LC-MS/MS comparison with synthetic standards or by NMR, as acyl glucuronide (M1), sulfoxide (M2), 25-hydroxy (a phenol, M3), 21-hydroxy (diastereomers of a benzylic alcohol, M5a and M5b), and 36-hydroxy (diastereomers of a methyl alcohol, M6a and M6b) analogs of montelukast [10].

Other interactions of GPM6A

• Chemotherapeutic regimens induced remission in all treated patients in the M6a and M6c groups but did not appear to affect the M6b group [1].

Analytical, diagnostic and therapeutic context of GPM6A

• We have isolated partial human cDNA and genomic clones encoding M6a and M6b and have characterized them by restriction mapping, Southern hybridization with cDNA probes, and sequence analysis [11].

References