Combined Targeting of JAK2 and Bcl-2/Bcl-xL to Cure Mutant JAK2-Driven Malignancies and Overcome Acquired Resistance to JAK2 Inhibitors

[1]  Brian J. Smith,et al.  Structure-guided design of a selective BCL-X(L) inhibitor. , 2013, Nature chemical biology.

[2]  K. Bhalla,et al.  Dual PI3K/AKT/mTOR Inhibitor BEZ235 Synergistically Enhances the Activity of JAK2 Inhibitor against Cultured and Primary Human Myeloproliferative Neoplasm Cells , 2013, Molecular Cancer Therapeutics.

[3]  L. Lam,et al.  ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets , 2013, Nature Medicine.

[4]  M. Loh,et al.  Targeting JAK1/2 and mTOR in murine xenograft models of Ph-like acute lymphoblastic leukemia. , 2012, Blood.

[5]  Ryan D. Morin,et al.  Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia. , 2012, Cancer cell.

[6]  A. Pardanani.  Ruxolitinib for myelofibrosis therapy: current context, pros and cons , 2012, Leukemia.

[7]  Erinna F. Lee,et al.  Bcl-2, Bcl-x(L), and Bcl-w are not equivalent targets of ABT-737 and navitoclax (ABT-263) in lymphoid and leukemic cells. , 2012, Blood.

[8]  B. Bernstein,et al.  Heterodimeric JAK-STAT Activation as a Mechanism of Persistence to JAK2 Inhibitor Therapy , 2011, Nature.

[9]  Eric Vangrevelinghe,et al.  Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90 inhibition , 2011, The Journal of experimental medicine.

[10]  A. Moliterno,et al.  Janus kinase inhibitors: an update on the progress and promise of targeted therapy in the myeloproliferative neoplasms , 2011, Current opinion in oncology.

[11]  S. Verstovsek,et al.  JAK2 inhibitors: are they the solution? , 2011, Clinical lymphoma, myeloma & leukemia.

[12]  P. Marynen,et al.  JAK2 rearrangements, including the novel SEC31A-JAK2 fusion, are recurrent in classical Hodgkin lymphoma. , 2009, Blood.

[13]  W. Vainchenker,et al.  Myeloproliferative neoplasm induced by constitutive expression of JAK2V617F in knock-in mice. , 2010, Blood.

[14]  J. Downing,et al.  Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of IKZF1, Hispanic/Latino ethnicity, and a poor outcome in pediatric B-progenitor acute lymphoblastic leukemia. , 2010, Blood.

[15]  Michael G. Kharas,et al.  Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietic stem and progenitor cells. , 2010, Cancer cell.

[16]  D. Tenen,et al.  Apoptosis induced by JAK2 inhibition is mediated by Bim and enhanced by the BH3 mimetic ABT-737 in JAK2 mutant human erythroid cells. , 2010, Blood.

[17]  E. Domany,et al.  Down syndrome acute lymphoblastic leukemia, a highly heterogeneous disease in which aberrant expression of CRLF2 is associated with mutated JAK2: a report from the International BFM Study Group. , 2010, Blood.

[18]  K. Shokat,et al.  Targeting the cancer kinome through polypharmacology , 2010, Nature Reviews Cancer.

[19]  J. Downing,et al.  Rearrangement of CRLF2 in B-progenitor– and Down syndrome–associated acute lymphoblastic leukemia , 2009, Nature Genetics.

[20]  A. Sharrocks.  Faculty Opinions recommendation of JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin. , 2009 .

[21]  Andrew J. Bannister,et al.  JAK2 phosphorylates histone H3Y41 and excludes HP1α from chromatin , 2009, Nature.

[22]  M. Loh,et al.  JAK mutations in high-risk childhood acute lymphoblastic leukemia , 2009, Proceedings of the National Academy of Sciences.

[23]  S. Verstovsek,et al.  Prospect of JAK2 inhibitor therapy in myeloproliferative neoplasms , 2009, Expert review of anticancer therapy.

[24]  A. Strasser,et al.  Unleashing the power of inhibitors of oncogenic kinases through BH3 mimetics , 2009, Nature Reviews Cancer.

[25]  J. O’Shea,et al.  Janus kinases in immune cell signaling , 2009, Immunological reviews.

[26]  R. Johnstone,et al.  Defining the target specificity of ABT-737 and synergistic antitumor activities in combination with histone deacetylase inhibitors. , 2009, Blood.

[27]  Jacqueline Sayyah,et al.  Jak2 inhibitors: Rationale and role as therapeutic agents in hematologic malignancies , 2009, Current oncology reports.

[28]  A. Tafuri,et al.  Activity of the BH3 mimetic ABT-737 on polycythemia vera erythroid precursor cells. , 2008, Blood.

[29]  D. Gilliland,et al.  TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations , 2007, Leukemia.

[30]  D. Gilliland,et al.  TG 101209 , a small molecule JAK 2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK 2 V 617 F and MPL W 515 L / K mutations , 2007 .

[31]  John Calvin Reed,et al.  Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. , 2006, Cancer cell.

[32]  S. Korsmeyer,et al.  An inhibitor of Bcl-2 family proteins induces regression of solid tumours , 2005, Nature.

[33]  Stefan N. Constantinescu,et al.  A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera , 2005, Nature.

[34]  Mario Cazzola,et al.  A gain-of-function mutation of JAK2 in myeloproliferative disorders. , 2005, The New England journal of medicine.

[35]  Sandra A. Moore,et al.  Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. , 2005, Cancer cell.

[36]  P. Campbell,et al.  Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders , 2005, The Lancet.

[37]  C. Dai,et al.  Increased erythropoiesis in polycythemia vera is associated with increased erythroid progenitor proliferation and increased phosphorylation of Akt/PKB. , 2005, Experimental hematology.

[38]  松山 智洋.  What's going on 造血器腫瘍 A gain-of-function mutation of JAK2 in myeloproliferative disorders. Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, Tichelli A, Cazzola M, Skoda RC. N Engl J Med. 2005; 352: 1779-90. PMID:15858187.--慢性骨髄増殖性疾患においてJAK2遺伝子の変異が高頻度にみられることを示した論文 , 2005 .

[39]  M. H. Nguyen,et al.  TEL-JAK2 constitutively activates the extracellular signal-regulated kinase (ERK), stress-activated protein/Jun kinase (SAPK/JNK), and p38 signaling pathways. , 2002, Blood.

[40]  M. H. Nguyen,et al.  TEL-JAK2 Mediates Constitutive Activation of the Phosphatidylinositol 3′-Kinase/Protein Kinase B Signaling Pathway* , 2001, The Journal of Biological Chemistry.

[41]  G. Meinhardt,et al.  STAT3 is constitutively active in some patients with Polycythemia rubra vera. , 2001, Experimental hematology.

[42]  O. Bernard,et al.  TEL-JAK2 transgenic mice develop T-cell leukemia. , 2000, Blood.

[43]  J. Aster,et al.  Transformation of hematopoietic cell lines to growth‐factor independence and induction of a fatal myelo‐ and lymphoproliferative disease in mice by retrovirally transduced TEL/JAK2 fusion genes , 1998, The EMBO journal.

[44]  C. Richard,et al.  Expression of Bcl-x in erythroid precursors from patients with polycythemia vera. , 1998, The New England journal of medicine.

[45]  R Berger,et al.  A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia. , 1997, Science.