Using functional genomics to overcome therapeutic resistance in hematological malignancies

Immunologic Research

Volumn 55, Issue 1-3, 2013, Pages 100-115

  Alvarez Calderon, Francesca ^a,b   Gregory, Mark A ^b   Degregori, James ^a,b,c  

^a DEPARTMENT OF MEDICINE   (United States)

^b UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^c University of Colorado Denver and Children s Hospital Colorado   (United States)

Author keywords

Hematological Malignancies; Leukemia; Lymphoma; RNAi; shRNA; Synthetic lethal screens; Targeted cancer therapy

Indexed keywords

DNA METHYLTRANSFERASE; GAMMA INTERFERON; IMATINIB; INTERLEUKIN 10; INTERLEUKIN 13; SHORT HAIRPIN RNA; SMALL INTERFERING RNA;

ACUTE LYMPHOBLASTIC LEUKEMIA; ARTICLE; B CELL LYMPHOMA; B LYMPHOCYTE ACTIVATION; BACTERIUM CULTURE; BLAST CELL CRISIS; BREAST CANCER; CANCER RESEARCH; CANCER THERAPY; CELL CYCLE CHECKPOINT; CHROMOSOME TRANSLOCATION; CHRONIC MYELOID LEUKEMIA; DNA DAMAGE; DNA REPLICATION; EPITHELIAL MESENCHYMAL TRANSITION; FOLLOW UP; FOOD AND DRUG ADMINISTRATION; FUNCTIONAL GENOMICS; GENE ACTIVATION; GENE AMPLIFICATION; GENE EXPRESSION; GENE EXPRESSION PROFILING; GENE MUTATION; GENE SILENCING; GENE TARGETING; GENETIC HETEROGENEITY; GLIOBLASTOMA; HUMAN; IN VITRO STUDY; IN VIVO STUDY; LARGE CELL LYMPHOMA; LEUKEMIA CELL; LUNG NON SMALL CELL CANCER; LYMPHOCYTE ACTIVATION; LYMPHOCYTE DIFFERENTIATION; LYMPHOCYTE MIGRATION; MYELODYSPLASTIC SYNDROME; PRIORITY JOURNAL; RNA INTERFERENCE; T LYMPHOCYTE ACTIVATION; TREATMENT FAILURE;

ANIMALS; DRUG RESISTANCE, NEOPLASM; GENOMICS; HEMATOLOGIC NEOPLASMS; HUMANS; RNA INTERFERENCE; RNA, SMALL INTERFERING;

EID: 84876742206     PISSN: 0257277X     EISSN: 15590755     Source Type: Journal    
DOI: 10.1007/s12026-012-8353-z     Document Type: Article

References (137)

1. Vardiman JW, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937-51.
2. Weinberg OK, et al. Clinical characterization of acute myeloid leukemia with myelodysplasia-related changes as defined by the 2008 WHO classification system. Blood. 2009;113(9):1906-8.
3. Campo E, et al. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011;117(19):5019-32.
4. Druker BJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. NEJM. 2001;344(14):1031-7.
5. Druker BJ. Translation of the Philadelphia chromosome into therapy for CML. Blood. 2008;112(13):4808-17.
6. Hughes TP, et al. Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS). Blood. 2010;116(19):3758-65.
7. Huang ME, et al. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988;72(2):567-72.
8. Sanz MA, et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2009;113(9):1875-91.
9. Alas S, Bonavida B. Rituximab inactivates signal transducer and activation of transcription 3 (STAT3) activity in B-non-Hodgkin's lymphoma through inhibition of the interleukin 10 autocrine/paracrine loop and results in down-regulation of Bcl-2 and sensitization to cytotoxic drugs. Cancer Res. 2001;61(13):5137-44.
10. Vega MI, et al. Rituximab (chimeric anti-CD20) sensitizes B-NHL cell lines to Fas-induced apoptosis. Oncogene. 2005;24(55):8114-27.
11. Vega MI, et al. Rituximab-induced inhibition of YY1 and Bcl-xL expression in Ramos non-Hodgkin's lymphoma cell line via inhibition of NF-kappa B activity: role of YY1 and Bcl-xL in Fas resistance and chemoresistance, respectively. J Immunol. 2005;175(4):2174-83.
12. Armstrong GT, et al. Late mortality among 5-year survivors of childhood cancer: a summary from the Childhood Cancer Survivor Study. J Clin Oncol. 2009;27(14):2328-38.
13. Reulen RC, et al. Long-term risks of subsequent primary neoplasms among survivors of childhood cancer. JAMA. 2011;305(22):2311-9.
14. Corbin AS, et al. Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity. J Clin Invest. 2011;121(1):396-409.
15. Hurtz C, et al. BCL6-mediated repression of p53 is critical for leukemia stem cell survival in chronic myeloid leukemia. J Exp Med. 2011;208(11):2163-74.
16. Mahon F-X, et al. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet oncol. 2010;11(11):1029-35.
17. Foà R, et al. Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2011;118(25):6521-8.
18. Schultz KR, et al. Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a children's oncology group study. J Clin Oncol. 2009;27(31):5175-81.
19. Mullighan CG, et al. BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros. Nature. 2008;453(7191):110-4.
20. Graham SM, et al. Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro. Blood. 2002;99(1):319-25.
21. Lemoli RM, et al. Molecular and functional analysis of the stem cell compartment of chronic myelogenous leukemia reveals the presence of a CD34- cell population with intrinsic resistance to imatinib. Blood. 2009;114(25):5191-200.
22. Kumari A, et al. Low BCR-ABL expression levels in hematopoietic precursor cells enable persistence of chronic myeloid leukemia under imatinib. Blood. 2012;119(2):530-9.
23. Agrawal SG, et al. Increased proteasomal degradation of Bax is a common feature of poor prognosis chronic lymphocytic leukemia. Blood. 2008;111(5):2790-6.
24. Konopleva M, et al. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell. 2006;10(5):375-88.
25. Paoluzzi L, et al. The BH3-only mimetic ABT-737 synergizes the antineoplastic activity of proteasome inhibitors in lymphoid malignancies. Blood. 2008;112(7):2906-16.
26. Paoluzzi L, et al. Targeting Bcl-2 family members with the BH3 mimetic AT-101 markedly enhances the therapeutic effects of chemotherapeutic agents in in vitro and in vivo models of B-cell lymphoma. Blood. 2008;111(11):5350-8.
27. Balakrishnan K, et al. AT-101 induces apoptosis in CLL B cells and overcomes stromal cell-mediated Mcl-1 induction and drug resistance. Blood. 2009;113(1):149-53.
28. Bélanger SD, St-Pierre Y. Role of selectins in the triggering, growth, and dissemination of T-lymphoma cells: implication of L-selectin in the growth of thymic lymphoma. Blood. 2005;105(12):4800-6.
29. Buchner M, et al. Spleen tyrosine kinase inhibition prevents chemokine- and integrin-mediated stromal protective effects in chronic lymphocytic leukemia. Blood. 2010;115(22):4497-506.
30. De Toni-Costes F, et al. A New alpha5beta1 integrin-dependent survival pathway through GSK3beta activation in leukemic cells. PLoS ONE. 2010;5(3):e9807.
31. Fenouille N, et al. Persistent activation of the Fyn/ERK kinase signaling axis mediates imatinib resistance in chronic myelogenous leukemia cells through upregulation of intracellular SPARC. Cancer Res. 2010;70(23):9659-70.
32. Bellodi C, et al. Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia chromosome-positive cells, including primary CML stem cells. J Clin Invest. 2009;119(5):1109-23.
33. Amrein L, et al. p53 and autophagy contribute to dasatinib resistance in primary CLL lymphocytes. Leukemia Res. 2011;35(1):99-102.
34. Quintas-Cardama A, Cortes J. Molecular biology of bcr-abl1-positive chronic myeloid leukemia. Blood. 2009;113(8):1619-30.
35. Sharma SV, et al. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell. 2010;141(1):69-80.
36. Braun T, et al. Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: a phase 2 trial. Blood. 2011;118(14):3824-31.
37. Lubbert M, et al. Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group. J Clin Oncol. 2011;29(15):1987-96.
38. Stathis A, et al. Phase I study of decitabine in combination with vorinostat in patients with advanced solid tumors and non-Hodgkin's lymphomas. Clin Cancer Res. 2011;17(6):1582-90.
39. Cashen AF, et al. Multicenter, phase II study of decitabine for the first-line treatment of older patients with acute myeloid leukemia. J Clin Oncol. 2010;28(4):556-61.
40. Issa JP, et al. Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2′-deoxycytidine (decitabine) in hematopoietic malignancies. Blood. 2004;103(5):1635-40.
41. Beck WT, Mueller TJ, Tanzer LR. Altered surface membrane glycoproteins in Vinca alkaloid-resistant human leukemic lymphoblasts. Cancer Res. 1979;39(6 Pt 1):2070-6.
42. Cole SP, et al. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science. 1992;258(5088):1650-4.
43. le Coutre P, et al. Induction of resistance to the Abelson inhibitor STI571 in human leukemic cells through gene amplification. Blood. 2000;95(5):1758-66.
44. Thomas J, et al. Active transport of imatinib into and out of cells: implications for drug resistance. Blood. 2004;104(12):3739-45.
45. White DL, et al. Most CML patients who have a suboptimal response to imatinib have low OCT-1 activity: higher doses of imatinib may overcome the negative impact of low OCT-1 activity. Blood. 2007;110(12):4064-72.
46. Aceves-Luquero CI, et al. ERK2, but not ERK1, mediates acquired and "de novo" resistance to imatinib mesylate: implication for CML therapy. PLoS ONE. 2009;4(7):e6124.
47. Delva L, et al. Resistance to all-trans retinoic acid (ATRA) therapy in relapsing acute promyelocytic leukemia: study of in vitro ATRA sensitivity and cellular retinoic acid binding protein levels in leukemic cells. Blood. 1993;82(7):2175-81.
48. Cornic M, et al. In vitro all-trans retinoic acid (ATRA) sensitivity and cellular retinoic acid binding protein (CRABP) levels in relapse leukemic cells after remission induction by ATRA in acute promyelocytic leukemia. Leukemia. 1994;8(6):914-7.
49. Ozpolat B, Mehta K, Lopez-Berestein G. Regulation of a highly specific retinoic acid-4-hydroxylase (CYP26A1) enzyme and all-trans-retinoic acid metabolism in human intestinal, liver, endothelial, and acute promyelocytic leukemia cells. Leuk Lymph. 2005;46(10):1497-506.
50. Gorre ME, et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science. 2001;293(5531):876-80.
51. Shah NP, Sawyers CL. Mechanisms of resistance to STI571 in Philadelphia chromosome-associated leukemias. Oncogene. 2003;22(47):7389-95.
52. Al-Ali HK, et al. High incidence of BCR-ABL kinase domain mutations and absence of mutations of the PDGFR and KIT activation loops in CML patients with secondary resistance to imatinib. Hematol J. 2004;5(1):55-60.
53. Muller MC, et al. Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR-ABL mutations. Blood. 2009;114(24):4944-53.
54. Sherbenou DW, et al. BCR-ABL SH3-SH2 domain mutations in chronic myeloid leukemia patients on imatinib. Blood. 2010;116(17):3278-85.
55. Roche-Lestienne C, et al. A mutation conferring resistance to imatinib at the time of diagnosis of chronic myelogenous leukemia. NEJM. 2003;348(22):2265-6.
56. Hofmann W-K, et al. Presence of the BCR-ABL mutation Glu255Lys prior to STI571 (imatinib) treatment in patients with Ph + acute lymphoblastic leukemia. Blood. 2003;102(2):659-61.
57. Willis SG, et al. High-sensitivity detection of BCR-ABL kinase domain mutations in imatinib-naive patients: correlation with clonal cytogenetic evolution but not response to therapy. Blood. 2005;106(6):2128-37.
58. Soverini S, et al. Philadelphia-positive patients who already harbor imatinib-resistant Bcr-Abl kinase domain mutations have a higher likelihood of developing additional mutations associated with resistance to second- or third-line tyrosine kinase inhibitors. Blood. 2009;114(10):2168-71.
59. Soverini S, et al. Philadelphia-positive acute lymphoblastic leukemia patients already harbor BCR-ABL kinase domain mutations at low levels at the time of diagnosis. Haematologica. 2011;96(4):552-7.
60. Bagrintseva K, et al. Mutations in the tyrosine kinase domain of FLT3 define a new molecular mechanism of acquired drug resistance to PTK inhibitors in FLT3-ITD-transformed hematopoietic cells. Blood. 2004;103(6):2266-75.
61. Moore AS, et al. Selective FLT3 inhibition of FLT3-ITD(+) acute myeloid leukaemia resulting in secondary D835Y mutation: a model for emerging clinical resistance patterns. Leukemia 2012.
62. Mullighan CG, et al. CREBBP mutations in relapsed acute lymphoblastic leukaemia. Nature. 2011;471(7337):235-9.
63. Bunn PA Jr. Can acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors be overcome by different small-molecule tyrosine kinase inhibitors? J Clin Oncol. 2007;25(18):2504-5.
64. Pao W, Chmielecki J. Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer. Nat Rev Cancer. 2010;10(11):760-74.
65. Kobayashi S, et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. NEJM. 2005;352(8):786-92.
66. Sequist LV, et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Trans Med 2011;3(75):75ra26.
67. Herbst RS, Bunn PA Jr. Targeting the epidermal growth factor receptor in non-small cell lung cancer. Clin Cancer Res. 2003;9(16 Pt 1):5813-24.
68. Engelman JA, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 2007;316(5827):1039-43.
69. Bean J, et al. MET amplification occurs with or without T790 M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. PNAS USA. 2007;104(52):20932-7.
70. Turke AB, et al. Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC. Cancer Cell. 2010;17(1):77-88.
71. Sosman JA, et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. NEJM. 2012;366(8):707-14.
72. Nazarian R, et al. Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature. 2010;468(7326):973-7.
73. Wagle N, et al. Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling. J Clin Oncol. 2011;29(22):3085-96.
74. Thomson S, et al. Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition. Cancer Res. 2005;65(20):9455-62.
75. Marusyk A, Polyak K. Tumor heterogeneity: causes and consequences. Biochim Biophys Acta. 2010;1805(1):105-17.
76. Anderson K, et al. Genetic variegation of clonal architecture and propagating cells in leukaemia. Nature. 2011;469(7330):356-61.
77. Gerlinger M, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. NEJM. 2012;366(10):883-92.
78. Snuderl M, et al. Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma. Cancer Cell. 2011;20(6):810-7.
79. Gerlinger M, Swanton C. How Darwinian models inform therapeutic failure initiated by clonal heterogeneity in cancer medicine. Brit J Cancer. 2010;103(8):1139-43.
80. Katayama R, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers. Sci Trans Med 2012;4(120):120ra17.
81. Doebele RC, et al. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res. 2012;18(5):1472-82.
82. Deininger MW, Goldman JM, Melo JV. The molecular biology of chronic myeloid leukemia. Blood. 2000;96(10):3343-56.
83. Notta F, et al. Evolution of human BCR-ABL1 lymphoblastic leukaemia-initiating cells. Nature. 2011;469(7330):362-7.
84. Ding L, et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature. 2012;481(7382):506-10.
85. Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Revs Genet. 2010;11(9):597-610.
86. Czech MP, Aouadi M, Tesz GJ. RNAi-based therapeutic strategies for metabolic disease. Nat Revs Endocrinol. 2011;7(8):473-84.
87. Kittler R, Buchholz F. Functional genomic analysis of cell division by endoribonuclease-prepared siRNAs. Cell Cycle. 2005;4(4):564-7.
88. Silva JM, et al. Second-generation shRNA libraries covering the mouse and human genomes. Nat Genet. 2005;37(11):1281-8.
89. Root DE, et al. Genome-scale loss-of-function screening with a lentiviral RNAi library. Nat Methods. 2006;3(9):715-9.
90. Moffat J, et al. A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen. Cell. 2006;124(6):1283-98.
91. Mullenders J, Bernards R. Loss-of-function genetic screens as a tool to improve the diagnosis and treatment of cancer. Oncogene. 2009;28(50):4409-20.
92. Scholl C, et al. Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells. Cell. 2009;137(5):821-34.
93. Barbie DA, et al. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature. 2009;462(7269):108-12.
94. Luo J, et al. A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. Cell. 2009;137(5):835-48.
95. Ngo VN, et al. A loss-of-function RNA interference screen for molecular targets in cancer. Nature. 2006;441(7089):106-10.
96. Whitehurst AW, et al. Synthetic lethal screen identification of chemosensitizer loci in cancer cells. Nature. 2007;446(7137):815-9.
97. Fotheringham S, et al. Genome-wide loss-of-function screen reveals an important role for the proteasome in HDAC inhibitor-induced apoptosis. Cancer Cell. 2009;15(1):57-66.
98. Gregory MA, et al. Wnt/Ca2 +/NFAT signaling maintains survival of Ph + leukemia cells upon inhibition of Bcr-Abl. Cancer Cell. 2010;18(1):74-87.
99. Burgess DJ, et al. Topoisomerase levels determine chemotherapy response in vitro and in vivo. PNAS USA. 2008;105(26):9053-8.
100. Hahn CK, et al. Proteomic and genetic approaches identify Syk as an AML target. Cancer Cell. 2009;16(4):281-94.
101. Pritchard JR, et al. Bcl-2 family genetic profiling reveals microenvironment-specific determinants of chemotherapeutic response. Cancer Res. 2011;71(17):5850-8.
102. Porter CC, et al. Integrated genomic analyses identify WEE1 as a critical mediator of cell fate and a novel therapeutic target in acute myeloid leukemia. Leukemia 2012;26(6):1266-76.
103. Gilliland DG, Jordan CT, Felix CA, The molecular basis of leukemia. Hematology/the education program of the american society of hematology. American Society of Hematology. Educ Prog, 2004;80-97.
104. Zuber J, et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature. 2011;478(7370):524-8.
105. Figueroa ME, et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell. 2010;18(6):553-67.
106. Fathi AT, Chabner BA. FLT3 inhibition as therapy in acute myeloid leukemia: a record of trials and tribulations. Oncologist. 2011;16(8):1162-74.
107. Astsaturov I, et al. Synthetic lethal screen of an EGFR-centered network to improve targeted therapies. Sci signal 2010;3(140):ra67.
108. Bivona TG, et al. FAS and NF-kappaB signalling modulate dependence of lung cancers on mutant EGFR. Nature. 2011;471(7339):523-6.
109. Casas-Selves M, et al. Tankyrase and the canonical Wnt pathway protect lung cancer cells from EGFR inhibition. Cancer Res. 72(16):4154-64.
110. Kim J, Tan AC. BiNGS!SL-seq: a bioinformatics pipeline for the analysis and interpretation of deep sequencing genome-wide synthetic lethal screen. Methods Mol Biol. 2012;802:389-98.
111. Sims D, et al. High-throughput RNA interference screening using pooled shRNA libraries and next generation sequencing. Genome Biol. 2011;12(10):R104.
112. Marcotte R, et al. Essential gene profiles in breast, pancreatic, and ovarian cancer cells. Cancer Disc. 2012;2:172-89.
113. Luo B, et al. Highly parallel identification of essential genes in cancer cells. PNAS USA. 2008;105(51):20380-5.
114. Konig R, et al. A probability-based approach for the analysis of large-scale RNAi screens. Nat Methods. 2007;4(10):847-9.
115. Kanehisa M, et al. The KEGG databases at GenomeNet. Nucleic Acids Res. 2002;30(1):42-6.
116. Luo T, et al. STK33 kinase inhibitor BRD-8899 has no effect on KRAS-dependent cancer cell viability. PNAS USA. 2012;109(8):2860-5.
117. Babij C, et al. STK33 kinase activity is nonessential in KRAS-dependent cancer cells. Cancer Res. 2011;71(17):5818-26.
118. Luo J, Solimini NL, Elledge SJ. Principles of cancer therapy: oncogene and non-oncogene addiction. Cell. 2009;136(5):823-37.
119. Lam LT, et al. Compensatory IKKalpha activation of classical NF-kappaB signaling during IKKbeta inhibition identified by an RNA interference sensitization screen. PNAS USA. 2008;105(52):20798-803.
120. Tyner JW, et al. RNAi screen for rapid therapeutic target identification in leukemia patients. PNAS USA. 2009;106(21):8695-700.
121. Jiang H, et al. A mammalian functional-genetic approach to characterizing cancer therapeutics. Nat Chem Biol. 2011;7(2):92-100.
122. Banerji V, et al. The intersection of genetic and chemical genomic screens identifies GSK-3α as a target in human acute myeloid leukemia. J Clin Invest. 2012;122(3):935-47.
123. Zhu YX, et al. RNAi screen of the druggable genome identifies modulators of proteasome inhibitor sensitivity in myeloma including CDK5. Blood. 2011;117(14):3847-57.
124. Tibes R, et al. RNAi screening of the kinome with cytarabine in leukemias. Blood 2012.
125. Meacham CE, et al. In vivo RNAi screening identifies regulators of actin dynamics as key determinants of lymphoma progression. Nat Genet. 2009;41(10):1133-7.
126. Bric A, et al. Functional identification of tumor-suppressor genes through an in vivo RNA interference screen in a mouse lymphoma model. Cancer Cell. 2009;16(4):324-35.
127. Zender L, et al. An oncogenomics-based in vivo RNAi screen identifies tumor suppressors in liver cancer. Cell. 2008;135(5):852-64.
128. Possemato R, et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature. 2011;476(7360):346-50.
129. Astier AL, et al. RNA interference screen in primary human T cells reveals FLT3 as a modulator of IL-10 levels. J Immunol. 2010;184(2):685-93.
130. Karlas A, et al. Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication. Nature. 2010;463(7282):818-22.
131. Konig R, et al. Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication. Cell. 2008;135(1):49-60.
132. Brass AL, et al. Identification of host proteins required for HIV infection through a functional genomic screen. Science. 2008;319(5865):921-6.
133. Paul P, et al. A Genome-wide multidimensional RNAi screen reveals pathways controlling MHC class II antigen presentation. Cell. 2011;145(2):268-83.
134. Solimini NL, Luo J, Elledge SJ. Non-oncogene addiction and the stress phenotype of cancer cells. Cell. 2007;130(6):986-8.
135. Witt AE, et al. Functional proteomics approach to investigate the biological activities of cDNAs implicated in breast cancer. J Proteome Res. 2006;5(3):599-610.
136. Hattori H, et al. RNAi screen identifies UBE2D3 as a mediator of all-trans retinoic acid-induced cell growth arrest in human acute promyelocytic NB4 cells. Blood. 2007;110(2):640-50.
137. Friedberg JW, et al. Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood. 2010;115(13):2578-85.