Disease relevance of MTX1

• A single nucleotide alteration in MTX1, 628T-->C, resulting in the amino acid change F202L, was identified in patients with Gaucher disease in association with the common N370S mutation in GBA [1].
• Human melanoma M21 cells were incubated at 0 degrees C or 37 degrees C with 10 microM free MTX or 10 microM MTX linked to one of the above carriers [2].
• Control mice administered 1 Gy with or without subsequent transplantation of normal marrow cells succumbed to MTX toxicity by day 45 [3].
• In acute lymphoblastic leukemia (ALL), central nervous system (CNS) prophylaxis with cranial irradiation plus 5 doses of intrathecal methotrexate (i.t. MTX) reduces the incidence of CNS relapse to 7%-15% [4].
• The use of cyclosporine-A/methotrexate (CyA/MTX) for graft-versus-host disease (GVHD) prophylaxis is safe and effective for patients undergoing allogeneic bone marrow transplantation after preparation with cyclophosphamide and total body irradiation [5].

Psychiatry related information on MTX1

• Two patients developed recurrent febrile upper respiratory infections in the Combi therapy group, while two had a single febrile infection in the MTX alone group [6].

High impact information on MTX1

• In a multiple regression analysis of B-lineage ALL, blast MTX-PG was significantly related to MTX dose (or plasma MTX concentration), lymphoblast ploidy (hyperdiploid > nonhyperdiploid), and percentage S-phase [7].
• Binding sites for MoAb 225.28S were more efficient for internalization of MTX than were those for the two polyclonal antibody preparations [2].
• Of 478 previously untreated patients who subsequently achieved an initial marrow remission, 299 were randomised to receive 2400 rad craniospinal radiation therapy (RT) or 2400 rad cranial RT plus intrathecal methotrexate (i.t. MTX) while the remaining 179 patients were randomised between the same two regimens using a radiation dose of 1800 rad [8].
• The presence of contiguous, highly homologous pseudogenes for both glucocerebrosidase and metaxin at the locus increases the likelihood of DNA rearrangements in this region [9].
• Since the same amino acid mutation in humans is associated with mild type 1 Gaucher disease, we suggest that metaxin protein is likely to be essential for embryonic development in mice [10].

Chemical compound and disease context of MTX1

• The incidence of hyperbilirubinemia (bilirubin greater than or equal to 2 mg/dL) increased from 48% to 80% (P = .02), and the mean maximal bilirubin increased from 4.67 +/- 7.27 to 8.72 +/- 8.73 mg/dL (P = .04), when CyA/MTX was used in place of CyA/MP for GVHD prophylaxis [5].
• Patients with delayed MTX clearance received additional leucovorin and experienced no severe toxicity [11].
• PURPOSE: During maintenance chemotherapy for childhood acute lymphoblastic leukemia (ALL), the cytotoxic metabolites of methotrexate (MTX polyglutamates) and mercaptopurine (6MP) (thioguanine nucleotides [6TGN]) accumulate intracellularly, including in erythrocytes (E-MTX and E-6TGN) with large interindividual variations [12].
• On the other hand, potentiation of MTX toxicity by purines was associated with substantial increases in deoxyadenosine 5'-triphosphate levels in conjunction with low deoxythymidine 5'-triphosphate levels [13].
• Using quantitative autoradiography, we investigated the entry over 90 min of [14C]methotrexate (MTX) into C6 gliomas implanted bilaterally into Wistar rat brains [14].

Biological context of MTX1

• Metaxin 1( MTX1) is a convergently transcribed gene contiguous to the 3' end of the GBA pseudogene [1].
• The metaxin genes of zebrafish have been investigated by determining the sequences of metaxin cDNAs and analyzing the translated amino acid sequences [15].
• We now report the genomic DNA sequence and organization of a 75-kb region around GBA, including the duplicated region containing GBA and MTX [16].
• MTX is 6 kb and consists of eight protein-encoding exons [17].
• Thus, there is a 278 amino acid open reading frame that is 97.8% identical to metaxin [17].

Anatomical context of MTX1

• A recently described protein, metaxin 1, serves as a component of a preprotein import complex in the outer membrane of the mammalian mitochondrion [18].
• The incidence of central nervous system (CNS) relapses following BM relapse was 19%, indicating that reprophylaxis to the CNS with IV/intrathecal (IT) MTX was insufficient [19].
• The modulation of MTX cytotoxicity by purines has been studied in a number of mammalian cell lines [13].
• During induced maturation of HL-60/LCV cells toward the granulocyte pathway, [3H]methotrexate (MTX) influx capacity and the amount of the affinity labeled transporter decreased rapidly in a parallel fashion [20].
• The major proteoglycan species identified in HT-29 MTX cells showed less acidic behavior than the proteoglycan isolated from HT-29 cells [21].

Associations of MTX1 with chemical compounds

• In the present paper, the utility of the combined solid-phase and solution approach is demonstrated by synthesizing muscarinic toxin 1 (MTX1) which binds to the muscarinic acetylcholine receptors [22].
• Metaxin is rich in leucine (14.2%) and in basic (12.9%) and acidic (12.0%) amino acids [17].
• It is also notable that only 2 (5%) of 39 patients who received the combination of methotrexate and cyclosporine (MTX/CSP) for the prevention of GVHD developed grade II acute GVHD, and none developed grades III to IV acute GVHD [23].
• A marked increase in hepatotoxicity was observed in 20 patients administered CyA/MTX, compared with 67 historical control patients who received CyA/methylprednisolone (CyA/MP) for GVHD prophylaxis with all other treatment and support variables remaining constant [5].
• During maintenance therapy the patients received daily oral thioguanine and biweekly intravenous (IV) MTX [19].

Other interactions of MTX1

• They are MEX1, MIX1, MTX1, MTX2, MTX3 and MTX4 [24].
• KD values of MTX for the DHFR in the K562/MTX-1 and -4 subclones also appeared to be altered relative to the parent cell line [25].
• Further, thymidylate synthase (TS) activity of the resistant subclones was reduced to 50% in K562/MTX-1 and -4 cells, and to 11-25% in the other subclones as compared to the parent cell line [25].
• Coexpression of metaxin with Tom20 had no further effect on the preprotein import [26].
• Exon A' is located in the TSP3/metaxin intergenic region, 1 kb 5' of exon A [27].

Analytical, diagnostic and therapeutic context of MTX1

• For patients in R2, event-free survival (pEFS) was 95% +/- 2% (n = 222) in NHL-BFM95 (MTX 1 g/m(2)) and 97% +/- 1% (n = 154) in NHL-BFM90 (MTX 5 g/m(2)) [28].
• Prophylactic intrathecal MTX therapy and splenectomy did not influence survival [29].
• Neoadjuvant MTX-containing chemotherapy was contraindicated in five patients (29%) due to age, cardiac insufficiency, or mental disorder [30].
• PURPOSE: To describe the use of combination chemotherapy, including divided-dose oral methotrexate (dMTX), for children with B-precursor acute lymphoblastic leukemia (ALL). dMTX produced prolonged MTX exposure on an outpatient basis [31].
• All patients were randomized to receive MTX during remission induction, either as CD-MTX (40 mg/m2) or HD-MTX (4 g/m2) with leucovorin rescue [32].

References