Main Article Content

Amit Samadhiya
Pratima Verma
Pushpendra Patel
Alpana Saxena


hsa-miR 17 ( Homo sapiens micro RNA 17 ), CML ( chronic myeloid leukemia ), Oncomir-1, micro RNA, RNA interference.


  1. Background: Chronic Myeloid Leukemia( CML) is the first disease to be linked to a specific gene alteration i.e. the BCR-ABL1 fusion gene.The BCR-ABL1 protein posseses a constitutively active tyrosine kinase activity,and Imatinib a tyrosine kinase inhibitor (TKI), is the first line treatment for CML. However Imatinib has been found unable to completely eliminate leukemic stem cells,which escape Imatinib induced apoptosis. Increased expression of MAPK pathway proteins in response to Imatinib therapy has been suggested as a probable cause of leukemic stem cells persistence. Oncomir-1 is a polycistronic micro RNA complex, which encodes six micro RNAs- miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1 and miR-92-1.  Increased oncomir-1 expression which regulates MAPK pathway at various levels, and directly regulates pre-apoptotic proteins containing BH domain, has been suggested as a reason for disease persistence and relapse of CML. This study evaluated the pathogenetic role of miR-17 component of miR-17-92 polycistron in CML.
  2. Objective – To measure the expression of microRNA 17 in peripheral blood leukocytes of newly diagnosed patients of Chronic Myeloid Leukemia and study the effect of standard care with Imatinib Mesylate on the expression level of  above miR.
  3. Study design – Hospital based Case-Control study.
  4. Setting – Department Of Biochemistry, Maulana Azad Medical College, New Delhi, Department Of Pathology, MAMC, New Delhi, Department of Medicine, LNJP Hospital, New Delhi.
  5. Subjects – 35 newly diagnosed CML cases in chronic phase of disease and 35 age and sex matched healthy controls.
  6. Methods – The expression of microRNA 17 in peripheral blood mononuclear cells (PBMCs) of  35 CML cases in chronic phase, in comparison to 35 age and sex matched healthy control subjects was carried out. RNA was extracted from PBMCs of  both CML patients and controls using Trizol reagent. Expression studies were performed by SYBR green based qRT-PCR and results were expressed as mean fold change. Expression of miR-17 was measured on two occasions i.e. in newly diagnosed untreated CML patients, and after 6 months of therapy with Imatinib.
  7. Result – The expression of miR-17 in PBMCs of untreated CML patients was up regulated with respect to healthy control subjects at statistically significant levels  (p<0.001). A re-evaluation of miR19b levels after six months treatment with Imatinib, revealed statistically significant down regulation of expression ,compared to the pre-therapy status(p <0.001).
Conclusion – The miR-17 functions as an oncomir in the pathogenesis of CML.The consistent down regulation of miR-17 expression in CML patients after Imatinib therapy, suggests that miR-17 could be a downstream component of BCR-ABL tyrosine kinase signaling pathway. The role of miR-17 in persistence of leukemic stem cells after theray with TKIs, needs to be further dissected.
Abstract 65 | PDF Downloads 5


1. Kurzrock R, Kantarjian HM, Druker BJ, Talpaz M. Philadelphia chromosome-positive leukemias: from basic mechanisms to molecular therapeutics. Ann Intern Med. 2003 May 20;138(10):819-30.

2. Schindler T, Bornmann W, Pellicena P, Miller WT, Clarkson B, Kuriyan J. Structural mechanismFor STI-571 inhibition of Abelson tyrosine kinase. Science. 2000sep 15; 289(5486):1938-42.

3. Graham SM, Jorgensen HG, Allan E, Pearson C, Alcorn MJ, Richmond L, Holyoake TL. Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemiaare insensitive to STI571 in vitro. Blood. 2002 Jan 1;99(1):319-25.

4. Bartel DP. MicroRNAs: target recognition and regulatory function. Cell. 2009 Jan;136(2):215–33

5. Hutvagner G, Zamore PD. A microRNA in a multiple-turnover RNAi enzyme complex. Science.2002;297(5589):2056–60.

6. Song JJ, Smith SK, Hannon GJ, Joshua-Tor L. Crystal structure of Argonaute and its implications for RISC slicer activity. Science. 2004;305(5689):1434–7.

7. Tanzer A, Stadler PF. Molecular evolution of a microRNA cluster. J Mol Biol. 2004 May 28;339(2):327-35.

8. Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, de Martino I et al. E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell. 2008 Mar;13(3):272-86.

9. Xiao C, Srinivasan L, Calado DP, Patterson HC, Zhang B, Wang J et al. Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol. 2008 Apr;9(4):405-14.

10. Ren R. Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia. Nat Rev Cancer. 2005 Mar;5(3):172-83.

11. MarjanYaghmaie. Archives of Iranian Medicine, Volume 11, Number 3, 2008: 247 – 51.

12. Bonauer A1, Dimmeler S. The microRNA-17-92 cluster: still a miRacle? Cell Cycle. 2009 Dec;8(23):3866-73. Epub 2009 Dec 4. 13. Ventura A, Young AG, Winslow MM, Lintault L, Meissner A, Erkeland SJ et al. Targeted deletion reveals essential and overlapping functions of the miR-17-92 family of miRNA clusters. Cell. 2008 Mar 7;132(5):875-86.

13. Ota A, Tagawa H, Karnan S, Tsuzuki S, Karpas A, Kira S et al. Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32amplification in malignant lymphoma. Cancer Res. 2004 May 1;64(9):3087-95.

14. Venturini L, Battmer K, Castoldi M, Schultheis B, Hochhaus A, Muckenthaler MU et al. Expression of the miR-17-92 polycistron in chronic myeloid leukemia (CML) CD34+ cells. Blood. 2007 May 15;109(10):4399-405.

15. O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature. 2005 Jun 9;435(7043):839-43.

16. Sawyers CL. Chronic myeloid leukemia. N Engl J Med. 1999;340:1330-40.

17. Kang ChD, Yoo SD, Hwanga BW, Kima KW, Kimc DW, Kima ChM, Kima SH, Chunga BS: The inhibition of ERK/MAPK not the activation of JNK/SAPK is primarily required to induce apoptosis in chronic myelogenousleukemic K562 cells. Leuk Res 2000, 24:527-34

18. Oda T, Heaney C, Hagopian JR, Okuda K, Griffin JD, Druker BJ. Crkl is the major tyrosine-phosphorylated protein in neutrophils from patients with chronic myelogenous leukemia. J Biol Chem. 1994 Sep 16;269(37):22925-8.

19. Senechal K, Halpern J, Sawyers CL. "The CRKL adaptor protein transforms fibroblasts and functions in transformation by the BCR-ABL oncogene". J BiolChem. 1996. 271 (38): 23255–61.

20. Shan SW, Lee DY, Deng Z, Shatseva T, Jeyapalan Z, Du WW, Zhang Y, Xuan JW, et. al. MicroRNA miR-17 retards tissue growth and represses fibronectin expression. Nat Cell Biol. 2009;11: 1031–38.