Page 205 - Haematologica March 2020
P. 205

Venetoclax response and maturation stage in AML
Acknowledgments
We thank the patients and donors who participated in the study. We appreciate critical comments and input from colleagues at FIMM (Dimitrios Tsallos, Jarno Kivioja, Riku Turkki, Komal Javarappa, Joseph Saad, Samuli Eldfors, Muntasir Mamun Majumder, Aleksandr Ianevski and Krister Wennerberg). We would like to thank the FIMM High Throughput Biomedicine Unit for preparing the drug plates (Laura Turunen, Jani Saarela), and the FIMM Sequencing Lab for preparing the exome sequence data. We also thank Alun Parsons, Minna Suvela and Siv Knaappila for their help in patient sample pro- cessing, and clinicians Riikka Räty, Eeva Martelin, Tuija Lundán, Sanna Siitonen, Minna Lehto, Juha Lievonen and Sari Kytölä for providing the samples.
Funding
This study was supported by grants from the European Research Council (M-IMM), Academy of Finland, Finnish Cancer Organizations, Finnish Cancer Institute, Emil Aaltonen Foundation, Sigrid Juselius Foundation, Orion Research Foundation, Instrumentarium Science Foundation, State Funding for University-Level Health Research in Finland, Relander Foundation, Gyllenberg Foundation, Ida Montin Foundation, Finnish Hematology Association and TEKES - the Finnish Funding Agency for Technology and Innovation.
References
1. Tauro S. The blind men and the AML ele- phant: can we feel the progress? Blood Cancer J. 2016;6(5):e424.
2. Döhner H, Weisdorf DJ, Bloomfield CD. Acute meloid leukemia. N Engl J Med. 2015;373(12):1136-1152.
3. Stone RM, Mandrekar SJ, Sanford BL, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017;377(5):454-464.
4. DiNardo CD, Stein EM, de Botton S, et al. Durable Remissions with ivosidenib in IDH1-mutated relapsed or refractory AML. N Engl J Med. 2018;378(25):2386-2398.
5. Stein EM, DiNardo CD, Pollyea DA, et al. Enasidenib in mutantIDH2relapsed or refractory acute myeloid leukemia. Blood. 2017;130(6):722-731.
6. Konopleva M, Pollyea DA, Potluri J, et al. Efficacy and biological correlates of response in a Phase II Study of venetoclax monotherapy in patients with acute myel- ogenous leukemia. Cancer Discov. 2016; 6(10):1106-1117.
7. DiNardo CD, Pratz K, Pullarkat V, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019;133(1):7-17.
8. Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol. 1976;33(4):451-458.
9. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3(7):730-737.
10. Riss TL, Moravec RA, Niles AL, et al. Cell viability assays. Eli Lilly & Company and the National Center for Advancing Translational Sciences.
11. Panoskaltsis N, Reid CDL, Knight SC. Quantification and cytokine production of circulating lymphoid and myeloid cells in acute myelogenous leukaemia1. Leukemia. 2003;17(4):716-730.
12. Carey A, Edwards DK, Eide CA, et al. Identification of interleukin-1 by functional screening as a key mediator of cellular expansion and disease progression in acute myeloid leukemia. Cell Rep. 2017;18(13): 3204-3218.
13. van der Schoot C, Jansen P, Poorter M, et al. Interleukin-6 and interleukin-1 production in acute leukemia with monocytoid differ- entiation. Blood. 1989;74(6):2081-2087.
14. Pemovska T, Kontro M, Yadav B, et al. Individualized systems medicine strategy to tailor treatments for patients with chemorefractory acute myeloid leukemia.
Cancer Discov. 2013;3(12):1416-1429.
15. Kontro M, Kumar A, Majumder MM, et al. HOX gene expression predicts response to BCL-2 inhibition in acute myeloid
leukemia. Leukemia. 2017;31(2):301-309. 16. Yadav B, Pemovska T, Szwajda A, et al. Quantitative scoring of differential drug sensitivity for individually optimized anti-
cancer therapies. Sci Rep. 2014;4:5193.
17. BLISS CI. The toxicity of poisons applied jointly11. Ann Appl Biol. 1939;26(3):585-
615.
18. Zhao W, Sachsenmeier K, Zhang L, Sult E,
Hollingsworth RE, Yang H. A new bliss independence model to analyze drug com- bination data. J Biomol Screen. 2014; 19(5):817-821.
19. Pölönen P, Mehtonen J, Lin J, et al. Hemap: An interactive online resource for charac- terizing molecular phenotypes across hematologic malignancies. Cancer Res. 2019;79(10):2466-2479.
20. Mehtonen J, Pölönen P, Häyrynen S, et al. Data-driven characterization of molecular phenotypes across heterogeneous sample collections. Nucleic Acids Res [Epub ahead of print].
21. Network TCGAR. Genomic and epige- nomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013; 368(22):2059-2074.
22. Tyner JW, Tognon CE, Bottomly D, et al. Functional genomic landscape of acute myeloid leukaemia. Nature. 2018; 562(7728):526-531.
23. Novershtern N, Subramanian A, Lawton LN, et al. Densely interconnected tran- scriptional circuits control cell states in human hematopoiesis. Cell. 2011;144(2): 296-309.
24. Salem M, Delwel R, Mahmoud LA, Clark S, Elbasousy EM, Löwenberg B. Maturation of human acute myeloid leukaemia in vitro: the response to five recombinant haematopoietic factors in a serum-free sys- tem. Br J Haematol. 1989;71(3):363-370.
25. Martínez-Cuadrón D, Gil C, Serrano J, et al. A precision medicine test predicts clini- cal response after idarubicin and cytarabine induction therapy in AML patients. Leuk Res. 2019;76:1-10.
26. Teh T-C, Nguyen N-Y, Moujalled DM, et al. Enhancing venetoclax activity in acute myeloid leukemia by co-targeting MCL1. Leukemia. 2018;32(2):303-312.
27. Glaser SP, Lee EF, Trounson E, et al. Anti- apoptotic Mcl-1 is essential for the develop- ment and sustained growth of acute myeloid leukemia. Genes Dev. 2012; 26(2):120-125.
28. Konopleva M, Milella M, Ruvolo P, et al. MEK inhibition enhances ABT-737-induced leukemia cell apoptosis via prevention of
ERK-activated MCL-1 induction and mod- ulation of MCL-1/BIM complex. Leukemia. 2012;26(4):778-787.
29. Wang JM, Chao JR, Chen W, Kuo ML, Yen JJ, Yang-Yen HF. The antiapoptotic gene mcl-1 is up-regulated by the phosphatidyli- nositol 3-kinase/Akt signaling pathway through a transcription factor complex con- taining CREB. Mol Cell Biol. 1999; 19(9):6195-206.
30. Shenoy AR, Kirschnek S, Häcker G. IL-15 regulates Bcl-2 family members Bim and Mcl-1 through JAK/STAT and PI3K/AKT pathways in T cells. Eur J Immunol. 2014;44(8):2500-2507.
31. Faderl S, Harris D, Van Q, Kantarjian HM, Talpaz M, Estrov Z. Granulocyte- macrophage colony-stimulating factor (GM-CSF) induces antiapoptotic and proapoptotic signals in acute myeloid leukemia. Blood. 2003;102(2):630-637.
32. Zhang H, Wilmot B, Bottomly D, et al. Biomarkers predicting venetoclax sensitivi- ty and strategies for venetoclax combina- tion treatment. Blood. 2018;132(Suppl 1):175.
33. White BS, Khan SA, Ammad-ud-din M, et al. Comparative Analysis of independent ex vivo functional drug screens identifies predictive biomarkers of BCL-2 inhibitor response in AML. Blood. 2018;132(Suppl 1):2763.
34. Tyner JW, Yang WF, Bankhead A, et al. Kinase Pathway Dependence in Primary Human Leukemias Determined by Rapid Inhibitor Screening. Cancer Res. 2013; 73(1):285-296.
35. Dietrich S, Oleś M, Lu J, et al. Drug-pertur- bation-based stratification of blood cancer. J Clin Invest. 2018;128(1):427-445.
36. Swords RT, Azzam D, Al-Ali H, et al. Ex- vivo sensitivity profiling to guide clinical decision making in acute myeloid leukemia: A pilot study. Leuk Res. 2018; 64:34-41.
37. Snijder B, Vladimer GI, Krall N, et al. Image-based ex-vivo drug screening for patients with aggressive haematological malignancies: interim results from a single- arm, open-label, pilot study. Lancet Haematol. 2017;4(12):e595-e606.
38. Pietarinen PO, Eide CA, Ayuda-Durán P, et al. Differentiation status of primary chronic myeloid leukemia cells affects sensitivity to BCR-ABL1 inhibitors. Oncotarget. 2017;8(14):22606-22615.
39. Niu X, Wang G, Wang Y, et al. Acute myeloid leukemia cells harboring MLL fusion genes or with the acute promyelo- cytic leukemia phenotype are sensitive to the Bcl-2-selective inhibitor ABT-199. Leukemia. 2014;28(7):1557-1560.
40. Pan R, Hogdal LJ, Benito JM, et al. Selective
haematologica | 2020; 105(3)
719


































































































   203   204   205   206   207