Background: Elevated JAK2V617F allele
burden is associated with enhanced expression of
downstream target genes in Philadelphia negative
chronic myeloproliferative neoplasms (CMPNs) which
include PV, ET & PMF. Previous studies have
shown the impact of JAK2V617F allele burden on
clinical phenotype of CMPNs. However, there is no
data from India regarding the association between
JAK2V617F allele burden and clinical phenotype in
PV. Aims/Settings and Design: We aimed to
investigate the effect of allele burden on
clinical phenotype in 90 JAK2V617F positive PV
patients and to see its influence on disease
related complications. Material and Methods:
Allele burden of 90 JAK2V617F positive PV patients
was quantified by Real-time polymerase chain
reaction (RQ-PCR). Results: 74/90 (82.22%) were
males and 16/90 (17.78%) were females (median 45
years, range 35-78). Patients with age >50
years had significantly higher JAK2V617F allele
burden (median 40.15%, range 0.49–91.62 %) than
patients with ≤ 50 years age (median 48.59 %,
range 0.56–86.74 %; P < 0.032). Patients with
splenomegaly had significantly higher JAK2V617F
allele burden (mean 50.24%, range 6.91–84.17%)
than patients without splenomegaly (mean 33.82 %,
range 0.49–71.83 %; P < 0.017). Patients with
higher allele burden (median 57.20, range
43.4–72.03%) had significantly raised thrombotic
events than the patients with lower allele burden
(median 37.38, range 0.49–84.17% P < 0.043).
49/90 (54%) were homozygous and 41/90 (46%) were
heterozygous. Conclusions: Higher JAK2V617F allele
burden showed association with increased age,
splenomegaly and thrombotic events. Thus, it may
be considered for prognostication and setting up
the treatment protocol in PV patients.
Genetic polymorphisms in the methylene tetrahydrofolate reductase (MTHFR) gene have been associated with the development of acute leukemias and various malignancies. The role of MTHFR polymorphism in the development of pediatric acute lymphoblastic leukemia (ALL) has been extensively studied among north Indians in various settings, yet its association with acute leukemias remains unresolved. To evaluate the relationship between functional MTHFR polymorphisms, C677T and A1298C and possible effect on risk of ALL in adults and children in North Indian population by comparing them with healthy controls. DNA was isolated from peripheral blood of 184 ALL patients (33 adults, 151 children) and 155 controls and analyzed by a PCR-restriction fragment length polymorphism assay. The frequency of MTHFR 677CT and 1298 AC genotypes were significantly lower among adult ALL cases when compared to the controls. We found a 1.74-fold reduced risk of ALL in individuals with 1298AC polymorphic variant and a 9.17-fold decreased risk of adult ALL. However, no statistically significant difference was evident between the above polymorphisms and susceptibility to ALL in children. Polymorphisms in the MTHFR gene possibly modulate risk of ALL in north Indian adults but not in children, although larger studies are needed.
Despite recent advances in the treatment of acute promyelocytic leukemia (APL), early mortality and relapses still occur. With the view to evaluate the role of FLT3 mutation in APL, 54 patients (median age 28 years, range11-57 years, male to female ratio 1.2:1, median TLC 8.4 x 10(9)/l, range 1-170 x 10(9)/l) were studied by reverse transcriptase-PCR. Forty-two patients (77%) achieved first remission (CR1). Ten (18.5%) of the 54 patients had internal tandem duplication of exons 11 and 12 of the FLT3 gene. The median TLC count was significantly higher in FLT3 positive cases (Median TLC 55.0 x 10(9)/l) as compared to FLT3 negative cases (Median TLC 6.8 x 10(9)/l) (p = 0.001). Induction CR was much lower (40%) in FLT3/ITD positive cases as compared to 86% of FLT3/ITD negative cases (p = 0.005). Early deaths too were significantly associated with FLT3/ITD positive cases (50 vs. 16% p = 0.033). The difference in the occurrence of bcr1 and bcr3 isoforms was not statistically significant between the two groups. The data suggest that the presence of FLT3/ITD in APL patients confers a poor prognosis.
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