top of page
Research Articles

      Abstract    

        

HOME

QUALITATIVE AND QUANTITATIVE ANALYSIS OF BILIARY CALCULI IN A TERTIARY CARE HOSPITAL

J Kaur, G Goyal, S Singh

 

ABSTRACT:

Background: FLT3 mutations are common genetic changes reported to have prognostic significance in acute leukemia. Fms-like tyrosine kisnase-3 (FLT3) belongs to class-III tyrosine kinase family and plays an important role in proliferation and differentiation of hematopoietic stem cells. The present study investigated the prevalence, distribution pattern in different cytogenetic groups and association with clinical parameters in Acute Lymphoblastic Leukaemia (ALL) patients. Methods: FLT3/ITD mutation was studied in Pre-B ALL (n=82) and Pre-T ALL (n=29) patients by PCR in exons 14 and 15 of FLT3 gene. Results: FLT3/ITD was detected in 7.3 % of Pre-B ALL patients. However, no FLT3/ITD mutation was detected in Pre-T ALL patients. Prevalence of FLT3/ITD (9.5%) among pediatric (<15 years) patients was high with normal cytogenetics (n=18). In patients with t (9:22) translocation (n=22) and hyperdiploidy (n=3), FLT3/ITD mutation was detected in 9.5% and 67% patients respectively. No statistical significant relationship was found between FLT3/ITD mutation and clinical features like age, WBC, PLT Count and Hb level. Conclusion: This is the first report investigating FLT3/ITD mutation prevalence in ALL patients from Pakistan. It is important to screen this mutation in certain cytogenetic subgroups of ALL patients to further assess their role in patient overall survival and targeted treatment therapy.

KEY WORDS: ALL, FLT3/ITD. Pakistan, PCR

REFERENCES:

  1. D, Levenstein M, Kim E, Carow C, Amin S, Rockwell P, et al. STK-1, the human homolog of Flk-2/Flt-3, is selectively expressed in CD34þ human bone marrow cells and is involved in the proliferation of early progenitor/stem cells. Proc Natl Acad Sci USA 1994; 91:459-63

  2. Nakao M, Yokota S, Iwai T, Kaneko H, Horiike S, Kashima K, et al. Internal tandem duplication of the gene found in acute myeloid leukemia. 1996; 10:1911-8.

  3. Gilliland DG, Griffin JD. The roles of in hematopoiesis and leukemia. Blood 2002 ; 100: 1532-42.

  4. Xu F, Taki T, Eguchi M, et al. Tandem duplication of the gene is infrequent in infant acute leukemia. Leukemia. 2000; 14:945-947

  5. Nakao M, Janssen JWG, Erz D, Seriu T, Bartram CR. Tandem duplication of the gene in acute lymphoblastic leukemia: a marker for the monitoring of minimal residual disease. Leukemia. 2000;14:522-524.

  6. Armstrong SA, Staunton JE, Silverman LB, et al. MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat Genet. 2002; 30:41-47.

  7. Andersson A, Paulsson K, Lilljebjorn H, Lassen C, Strombeck B, Heldrup J, Behrendtz M, Johansson B, Fioretos T: mutations in a 10 year consecutive series of 177 childhood acute leukemias and their impact on global gene expression patterns. Genes Chromosomes Cancer 2008; 47:64-70.

  8. Braoudaki M, Karpusas M, Katsibardi K, Papathanassiou C, Karamolegou K, Tzortzatou-Stathopoulou F: Frequency of mutations in childhood acute lymphoblastic leukemia. Med Oncol 2009; 26:460-462.

  9. Paietta E, Ferrando AA, Neuberg D, Bennett JM, Racevskis J, Lazarus H, Dewald G, Rowe JM, Wiernik PH, Tallman MS, Look AT. Activating mutations in CD117/KIT(+) T-cell acute lymphoblastic leukemias. Blood. 2004;104:558-60.

  10. Weisberg E, Barrett R, Liu Q, Stone R, Gray N, Griffin JD: inhibition and mechanisms of drug resistance in mutant FLT3-positive AML. Drug Resist Update 2009:12:81-89.

  11. Kiyoi, H., Naoe, T., Nakano, Y., Yokota, S., Minami, S., Miyawaki, S., Akiyama, H. Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. Blood 1999; 93: 3074-3080.

  12. Elyamany GH, Awad M, Fadalla K, Al-Balawi M , Al- Abulaaly A. Frequency and prognostic relevance of Mutations in Saudi Acute Myeloid Leukemia Patients. Adv Hematol. 2014; 2014:141-360

  13. Ishfaq M, Malik A, Faiz M., Sheikh I A, Asif M, Khan MN, Qazi MH. Molecular characterization of mutations in acute leukemia patients.. 2012; 4581-4585.

  14. Andersson A, Paulsson K, Lilljebjörn H, Lassen C , Strömbeck B, Heldrup J, Fioretos T. mutations in a 10 year consecutive series of 177 childhood acute leukemias and their impact on global gene expression patterns.2008;: 64-70.

  15. Xu F, Taki T, Yang H W, Hanada R, Hongo T, Ohnishi H, Hayashi Y.Tandem duplication of the gene is found in acute lymphoblastic leukaemia as well as acute myeloid leukaemia but not in myelodysplastic syndrome or juvenile chronic myelogenous leukaemia in children.. 1999;: 155-162.

  16. Chang P, Kang M, Xiao A, Chang J, Feusner J, Buffler P, Jemels, J. mutation incidence and timing of origin in a population case series of pediatric leukemia.. 2010;: 513.

  17. Yamamoto T, Isomura M, Xu Y, Liang J, Yagasaki, H, Kamachi, Y, Kojma S. PTPN11, and mutations in childhood acute lymphoblastic leukemia.2006; : 1085-1089.

  18. Taketani, T., Taki, T., Sugita, K., Furuichi, Y., Ishii, E., Hanada, R., Hayashi, Y. mutations in the activation loop of tyrosine kinase domain are frequently found in infant ALL with MLL rearrangements and pediatric ALL with hyperdiploidy.2004;: 1085-1088.

  19. Grossmann V, Haferlach C, Weissmann S, Roller A, Schindela S, Poetzinger F, Stadler K, Bellos F, Kern W, Haferlach T, Schnittger S, Kohlmann A. The molecular profile of adult T-cell acute lymphoblastic leukemia: Mutations in RUNX1 and DNMT3A are associated with poor prognosis in T-ALL. Genes Chromosomes Cancer. 2013 ;52:410-22

bottom of page