17 research outputs found
Analysis of candidate molecular targets in adult (CML) and childhood (AML, ALL) Leukemias
Cataloged from PDF version of article.Candidate molecular targets were investigated in three different types of
leukemias, chronic myeloid leukemia (CML), acute myeloid leukemia (AML) and
acute lymphocytic leukemia (ALL). The first group of these molecular targets was
identified through a cDNA based gene expression profile analysis in sixty-seven
CML patients who were classified according to clinical parameters known as new
prognostic score (NPS). CML patients can be divided into three groups of low-risk,
intermediate-risk, and high-risk, based on NPS. Response of these risk groups to
treatment is not uniform and the gene expression profiles associated with each risk
group remain unknown. Seven genes were chosen from a cDNA microarray study in
which two high versus two low-risk patients were analyzed. Semi-quantitative and
real-time reverse transcription polymerase chain reaction (RT-PCR) analysis of these
differentially expressed transcripts highly correlated with the microarray data.
Expression levels of all genes, except PTGS1, were significantly different between
the high (n=9) and low-risk (n=7) CML by semi-quantitative RT-PCR (IFITM1 and
CXCL3 p=0.001; CCNH p=0.012; RAB1A p=0.01, PRKAR2B p=0.016; UCP2
p=0.04; and PTGS1 p=0.315). Real-time RT-PCR analysis showed similar results
for IFITM1 expression in thirty-four low and eleven high-risk patients (p=9.7976 x
10-11). Higher IFITM1 or lower CXCL3 expression correlated with improved
survival (p=0.01 and p=0.059 respectively). Gene expression profiling is a valuable
tool to identify candidate risk group indicator genes for the development of a
molecular classification system for CML, which may also predict survival.
Although the connection between DNA-repair gene mutations and
hematological malignancies are now well established, germ-line mutations in the
base excision repair (BER) pathway was only recently documented in an inherited
cancer syndrome in human homologue of E. coli mut Y (MYH). Interestingly, the
cancer associated MYH missense mutations Tyr165Cys and Gly382Asp have been
documented with a high frequency (1 percent) in a control group of the British
population. Therefore, we screened the above mentioned missense variants in two
different childhood leukemias, AML (n=45) and ALL (n=140). Neither mutation was
present in any of the patient samples and controls, except for one patient diagnosed
with AML/M3. Tyr165Cys mutation in the heterozygous state was present in the
sample obtained at the time of initial diagnosis. Further sampling, at remission, and
the analysis of parental DNA, showed only the normal allele. Therefore, the
mutation was considered to be specific for the leukemic blasts. Based on these
results, an association between childhood leukemias and the MYH missense variants
Tyr165Cys and Gly382Asp was not observed. Also, these variants appear to be
absent -if not at a very low frequency- in the Turkish population, contrary to the
British population.Boylu, Cemaliye AkyerliPh.D
Disturbed X-chromosome inactivation mosaicism in females with scleroderma
68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals -- OCT 16-21, 2004 -- San Antonio, TXWOS: 000223799001723…Amer Coll Rheumatol, Assoc Rheumatol Hlth Profes
Skewed X chromosome inactivation in scleroderma: comment on the article by Ozbalkan et al - Reply
WOS: 000233285400051