Lack of fragile histidine triad protein has been reported in leukemia.
Could we suspect that reduced histidine levels may result in reduced levels of these proteins.
Could histidine supplements restore protein availability?
1: Oncogene 1999 Jan 7;18(1):79-85
Aberrant FHIT mRNA transcripts are present in malignant and normal haematopoiesis, but absence of FHIT protein is restricted to leukaemia.
Peters UR, Hasse U, Oppliger E, Tschan M, Ong ST, Rassool FV, Borisch B, Tobler A, Fey MF.
Department of Clinical Research, the Institute of Medical Oncology, University and Inselspital, Berne, Switzerland.
Aberrant FHIT mRNA transcripts are present in malignant and normal haematopoiesis, but absence of FHIT protein is restricted to leukaemia Alterations of the recently cloned fragile histidine! triad (FHIT) gene at chromosome 3p14.2 are frequent in a variety of solid tumours and cancer cell lines. Based on these findings, FHIT has been proposed as a putative tumour-suppressor gene. We evaluated the mRNA expression of the FHIT gene in samples from 55 patients with various haematological malignancies (21 AML, 8 CML, 10 CLL, seven low-grade and nine high-grade Non-Hodgkin's lymphomas), in a panel of 16 leukaemia cell lines, in normal mature haematopoietic cells of both myeloid and lymphoid lineage, as well as in CD34+ haematopoietic progenitor cells. Aberrant FHIT mRNA transcripts were observed in 14/16 (88%) leukaemia cell lines, 43/55 (78%) primary haematological neoplasms, but also in 17/22 (77%) normal controls. 1/16 (6%) cell lines and 7/55 (13%) neoplasms did not express any FHIT mRNA. cDNA sequencing revealed exonic deletions, small DNA insertions and combinations of both. Analysis of genomic DNA showed gene deletions in two myeloid leukaemia ce! ll lines. In contrast to all normal types of haematopoietic cells, FH IT protein was clearly reduced or absent in 8/18 (44%) neoplastic samples tested. Our data indicate that whilst aberrant FHIT mRNA transcripts are seen both in normal and malignant cells, lack of FHIT protein is restricted to leukaemia. Absent FHIT protein expression might contribute to leukaemogenesis.
PMID: 9926922 [PubMed - indexed for MEDLINE]
1: J Neural Transm Suppl 2001;(61):347-59
Reduction of nucleoside diphosphate kinase B, Rab GDP-dissociation inhibitor beta and histidine triad nucleotide-binding protein in fetal Down syndrome brain.
Weitzdoerfer R, Stolzlechner D, Dierssen M, Ferreres J, Fountoulakis M, Lubec G.
Department of Pediatrics, University of Vienna, Austria.
Information on the various factors leading to impairments in the developing brain of fetal Down Syndrome patients is limited to few histological reports. We therefore attempted to describe expression levels of proteins in brain using the proteomic technique of two-d! imensional electrophoresis with subsequent mass spectroscopical identification of protein spots and quantification with specific software. Cortical tissue was obtained from autopsy of human fetal abortus. Protein levels of GTP-binding nuclear protein ran, guanine nucleotide-binding protein g(o), alpha subunit 2, guanine nucleotide-binding protein g(i)/g(s)/g(t) beta subunit 1, -beta subunit 2, guanine nucleotide-binding protein beta subunit 5, nucleoside diphosphate kinase A, nucleoside diphosphate kinase B, Rab GDP-dissociation inhibitor beta, Rho GDP-dissociation inhibitor 1, biphosphate 3'- nucleotidase, small glutamine-rich tetra-tricopeptide repeat-containing protein and histidine triad nucleotide-binding protein were studied. Quantification revealed statistically significant reduced levels of nucleoside diphosphate kinase B, Rab GDP-dissociation inhibitor beta and histidine triad nucleotide-binding protein in fetal DS brain as compared to controls. We co! nclude that in early prenatal life proteins involved in neural differ entiation, migration and synaptic transmission are impaired in DS cortex. These results may help to understand the abundant mechanisms leading to abnormalities in the wiring, structure and function of DS brain.
PMID: 11771757 [PubMed - indexed for MEDLINE]
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