{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T15:16:22Z","timestamp":1789398982246,"version":"build-2803163510"},"reference-count":113,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,7,31]],"date-time":"2017-07-31T00:00:00Z","timestamp":1501459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:p>\n                    Despite recent progress in the understanding of the molecular basis of acute leukemias, treatment options for these diseases have not changed significantly over the last few decades. We present a nonexhaustive summary of the current cytogenetic and molecular changes associated with acute leukemias in disease prognostication and potential targeted therapies. An emerging paradigm is that many genetic or molecular alterations target similar signal transduction, transcriptional, and epigenetic pathways. Some of these targets may be used as predictive biomarkers for the development of novel targeted therapies that depart significantly from conventional chemotherapy, the current mainstay for the treatment of acute leukemias. Established leukemia\u2010specific predictive biomarkers for precision medicine include those genetic lesions such as\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">BCR<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">ABL<\/jats:styled-content>\n                      1\n                    <\/jats:italic>\n                    for Philadelphia\u2010positive acute lymphoblastic leukemia and\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">RAR<\/jats:styled-content>\n                    <\/jats:italic>\n                    \u03b1 for acute promyelocytic leukemia. Evidence indicates that targeted therapy for\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">FLT<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">ITD<\/jats:styled-content>\n                    <\/jats:italic>\n                    gene mutations with small\u2010molecule tyrosine kinase inhibitors can extend its use from relapsed disease to up\u2010front induction therapy. Core\u2010binding factor\n                    <jats:styled-content style=\"fixed-case\">acute myeloid leukemia<\/jats:styled-content>\n                    in adults predicts benefit with high\u2010dose cytarabine in the absence of\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">KIT<\/jats:styled-content>\n                    <\/jats:italic>\n                    mutation. Although risk\u2010adapted therapy based on genetic abnormalities in acute leukemias has allowed the beginning of personalized treatment and selective use of hematopoietic stem cell transplantation, the prognostic and\/or predictive value of many novel mutations of the acute leukemic genome is yet to be elucidated. Many challenges lie ahead in targeted therapies due to overlapping of chromosomal and molecular lesions as well as other limiting factors. Future work should focus on the understanding of pathogenetic changes that lead to leukemogenesis, which may guide the rational design of new targeted therapies and make the drive toward precision medicine for acute leukemias one step closer.\n                  <\/jats:p>","DOI":"10.1002\/phar.1977","type":"journal-article","created":{"date-parts":[[2017,6,27]],"date-time":"2017-06-27T08:48:56Z","timestamp":1498553336000},"page":"1052-1072","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Driving Toward Precision Medicine for Acute Leukemias: Are We There Yet?"],"prefix":"10.1002","volume":"37","author":[{"given":"Clement","family":"Chung","sequence":"first","affiliation":[{"name":"Lyndon B. Johnson General Hospital Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilary","family":"Ma","sequence":"additional","affiliation":[{"name":"MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-007-0253-2"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-04-1199"},{"key":"e_1_2_9_4_1","unstructured":"National Comprehensive Cancer Network (NCCN).Clinical practice guidelines in acute myeloid leukemia. V2.2016. Available fromhttp:\/\/www.nccn.org. Accessed November 30 2016."},{"key":"e_1_2_9_5_1","unstructured":"National Comprehensive Cancer Network (NCCN).Clinical practice guidelines in acute lymphoblastic leukemia. V2.2016. Available fromhttp:\/\/www.nccn.org. Accessed November 30 2016."},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21948"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(86)92674-7"},{"key":"e_1_2_9_8_1","first-page":"109","article-title":"Identification of a translocation with quinacrine fluorescence in a patient with acute leukemia","volume":"16","author":"Rowley JD","year":"1973","journal-title":"Ann Genet"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1592"},{"key":"e_1_2_9_10_1","first-page":"932","article-title":"Treatment of refractory AML","volume":"10","author":"Estey E","year":"1996","journal-title":"Leukemia"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10738"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V88.2.756.bloodjournal882756"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808253"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-11-185132"},{"key":"e_1_2_9_15_1","doi-asserted-by":"crossref","DOI":"10.1182\/blood.V124.21.796.796","article-title":"Favorable outcomes for older adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL): early results of U.S. intergroup trial C10403 [abstract 796]","author":"Stock W","year":"2014","journal-title":"Blood"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/421723"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.05.049"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3665"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1259037"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2821"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.05.047"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.05.010"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2003.1.82"},{"key":"e_1_2_9_24_1","first-page":"1254","article-title":"Effect of postremission chemotherapy before human leukocyte antigen\u2010identical sibling transplantation for acute myelogenous leukemia in first complete remission","volume":"96","author":"Tallman MS","year":"2000","journal-title":"Blood"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2000.02178.x"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.30.1820"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90112-C"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V72.2.567.567"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401448"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.4.1083.bloodjournal8541083"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404188"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-8722-2-23"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-05-2174"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.12450"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2011.06.003"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-368225"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112304"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-03-343988"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.55"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-03-419622"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.243"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1053\/shem.2002.36921"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197806)41:6<2484::AID-CNCR2820410659>3.0.CO;2-#"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc969"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121484"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25670"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-08-3167"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24072"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-03-0867"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.30.7926"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(02)00069-7"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.11.3885"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-07-2307"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-01-266742"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-261867"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1320661111"},{"key":"e_1_2_9_57_1","doi-asserted-by":"crossref","unstructured":"CortesJ PerlAE DombretH et al.Final results of a phase 2 open\u2010label monotherapy efficacy and safety study of quizartinib (AC220) in patients \u2265 60 years old with FLT3 ITD positive or negative relapsed\/refractory acute myeloid leukemia [abstract 48]. Paper presented at: 2012 Annual Meeting of American Society of Hematology (ASH) Atlanta GA December 8\u201012 2012.","DOI":"10.1182\/blood.V120.21.48.48"},{"key":"e_1_2_9_58_1","doi-asserted-by":"crossref","unstructured":"StoneRM MandrekarS SanfordBL et al.Blood. 2015; 126:6. The multi\u2010kinase inhibitor midostaurin (M) prolongs survival compared with placebo (P) in combination with daunorubicin (D)\/cytarabine (C) induction (ind) high\u2010dose C consolidation (consol) and as maintenance (maint) therapy in newly diagnosed acute myeloid leukemia (AML) patients (pts) age 18\u201060 with FLT3 mutations (muts): an international prospective randomized (rand) P\u2010controlled double\u2010blind trial (CALGB 10603\/RATIFY [Alliance]). Paper presented at: 57th ASH Annual Meeting Orlando FL December 5\u20108 2015.","DOI":"10.1182\/blood.V126.23.6.6"},{"key":"e_1_2_9_59_1","first-page":"855","article-title":"Targeting epigenetic changes in acute myeloid leukemia","volume":"3","author":"Blum W","year":"2005","journal-title":"Clin Adv Hematol"},{"key":"e_1_2_9_60_1","article-title":"Impact of molecular mutations on treatment response to hypomethylating agents in MDS [abstract 461]","author":"Traina F","year":"2011","journal-title":"ASH Ann Meeting"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-08-3522"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-235358"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2012.150"},{"key":"e_1_2_9_64_1","first-page":"2","article-title":"Histone deacetylase\u2010targeted treatment restores retinoic acid signaling and differentiation in acute myeloid leukemia","volume":"61","author":"Ferrara EF","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.276"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23795"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70281-5"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07417.x"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.3.547"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.07.116"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-01-130237"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.13.7265"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.02.053"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-116186"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70066-8"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1705904"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2015.8"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2253"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11899-014-0210-9"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404302"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22163"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-09-377713"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-09-529008"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70377-7"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-03-0717"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2008.10.001"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.47.6770"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-10-462358"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.55.4105"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-09-245944"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-1528"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1403088"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.48.5292"},{"key":"e_1_2_9_94_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.924"},{"key":"e_1_2_9_95_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1636"},{"key":"e_1_2_9_96_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-12-389932"},{"key":"e_1_2_9_97_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0208"},{"key":"e_1_2_9_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.06.009"},{"key":"e_1_2_9_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2007.03.009"},{"key":"e_1_2_9_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)71170-2"},{"key":"e_1_2_9_101_1","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1182\/blood.V126.23.1328.1328","article-title":"A phase 1 study of denintuzumab mafodotin (SGN\u2010CD19A) in adults with relapsed or refractory B\u2010lineage acute leukemia (B\u2010ALL) and highly aggressive lymphoma","volume":"126","author":"Fathi AT","year":"2015","journal-title":"Blood"},{"key":"e_1_2_9_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2015.12.004"},{"key":"e_1_2_9_103_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2011.08.001"},{"key":"e_1_2_9_104_1","doi-asserted-by":"crossref","DOI":"10.1200\/jco.2014.32.15_suppl.7065","article-title":"Phase II study of the hyper\u2010CVAD regimen in combination with ofatumumab as frontline therapy for adults with CD\u201020 positive acute lymphoblastic leukemia [abstract 7065]","volume":"32","author":"Jabbour E","year":"2014","journal-title":"J Clin Oncol"},{"key":"e_1_2_9_105_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13764"},{"key":"e_1_2_9_106_1","unstructured":"KantarjianHM DeAngeloDJ AdvaniAS et al.Overall survival in relapsed\/refractory B\u2010cell acute lymphoblastic leukemia patients receiving inotuzumab ozogamicin vs standard care in the phase 3 INO\u2010VATE study[abstract LB2233]. Paper presented at: 2016 Congress of the European Hematology Association Congress Copenhagen Denmark June 9\u201012 2016."},{"key":"e_1_2_9_107_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509277"},{"key":"e_1_2_9_108_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V71.5.1480.1480"},{"key":"e_1_2_9_109_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22209"},{"key":"e_1_2_9_110_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403422"},{"key":"e_1_2_9_111_1","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1182\/blood.V108.11.2293.2293","article-title":"CD52 Expression in adult acute lymphoblastic leukemia (ALL): quantitative flow cytometry provides new insights","volume":"108","author":"Lozanski G","year":"2006","journal-title":"Blood"},{"key":"e_1_2_9_112_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2930633"},{"key":"e_1_2_9_113_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1113205"},{"key":"e_1_2_9_114_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-02-337261"}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fphar.1977","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/phar.1977","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T10:05:43Z","timestamp":1761041143000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1002\/phar.1977"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,31]]},"references-count":113,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2017,9]]}},"alternative-id":["10.1002\/phar.1977"],"URL":"https:\/\/doi.org\/10.1002\/phar.1977","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"value":"0277-0008","type":"print"},{"value":"1875-9114","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,31]]},"assertion":[{"value":"2017-07-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}