Targeting the IDH2 Pathway in Acute Myeloid Leukemia

被引：29

作者：

Amaya, Maria L. ^{[1
]}

Pollyea, Daniel A. ^{[2
]}

机构：

[1] Univ Colorado, Div Med Oncol, Aurora, CO 80224 USA

[2] Univ Colorado, Div Hematol, Aurora, CO 80224 USA

来源：

CLINICAL CANCER RESEARCH | 2018年 / 24卷 / 20期

关键词：

ISOCITRATE-DEHYDROGENASE; 1; ONCOMETABOLITE; 2-HYDROXYGLUTARATE; PROGNOSTIC-SIGNIFICANCE; GEMTUZUMAB OZOGAMICIN; SUPPORTIVE CARE; OLDER PATIENTS; MUTANT IDH2; MUTATIONS; OPEN-LABEL; SURVIVAL;

D O I：

10.1158/1078-0432.CCR-18-0536

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Acute myeloid leukemia (AML) is an aggressive disease with a poor prognosis. A large percentage of patients succumb to this disease in spite of aggressive treatments with chemotherapy. Recent advances with mutational analysis led to the discovery of isocitrate dehydrogenase (IDH) mutations in AML. IDH2 is an enzyme that catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate; its mutated version leads to the accumulation of the oncometabolite (R)-2 hydroxyglutarate, which disrupts several cell processes and leads to a blockage in differentiation. Targeting IDH2 is compelling, as it is an early and stable mutation in AML. Enasidenib, a specific smallmolecule inhibitor of IDH2, recently gained FDA approval for the treatment of patients with relapsed/refractory IDH2-mutated AML. In this review, we will focus on the indications and efficacy of enasidenib in the treatment of patients with IDH2-mutated AML. (C) 2018 AACR.

引用

页码：4931 / 4936

页数：6

共 61 条

[1] Acquired mutations in the genes encoding IDH1 and IDH2 both are recurrent aberrations in acute myeloid leukemia: prevalence and prognostic value [J].

Abbas, Saman ;

Lugthart, Sanne ;

Kavelaars, Francois G. ;

Schelen, Anita ;

Koenders, Jasper E. ;

Zeilemaker, Annelieke ;

van Putten, Wim J. L. ;

Rijneveld, Anita W. ;

Lowenberg, Bob ;

Valk, Peter J. M. .

BLOOD, 2010, 116 (12) :2122-2126

[2] The Bcl-2 apoptotic switch in cancer development and therapy [J].

Adams, J. M. ;

Cory, S. .

ONCOGENE, 2007, 26 (09) :1324-1337

[3] Gemtuzumab Ozogamicin Versus Best Supportive Care in Older Patients With Newly Diagnosed Acute Myeloid Leukemia Unsuitable for Intensive Chemotherapy: Results of the Randomized Phase III EORTC-GIMEMA AML-19 Trial [J].

Amadori, Sergio ;

Suciu, Stefan ;

Selleslag, Dominik ;

Aversa, Franco ;

Gaidano, Gianluca ;

Musso, Maurizio ;

Annino, Luciana ;

Venditti, Adriano ;

Voso, Maria Teresa ;

Mazzone, Carla ;

Magro, Domenico ;

De Fabritiis, Paolo ;

Muus, Petra ;

Alimena, Giuliana ;

Mancini, Marco ;

Hagemeijer, Anne ;

Paoloni, Francesca ;

Vignetti, Marco ;

Fazi, Paola ;

Meert, Liv ;

Ramadan, Safaa Mahmoud ;

Willemze, Roel ;

de Witte, Theo ;

Baron, Frederic .

JOURNAL OF CLINICAL ONCOLOGY, 2016, 34 (09) :972-+

[4] Enasidenib induces acute myeloid leukemia cell differentiation to promote clinical response [J].

Amatangelo, Michael D. ;

Quek, Lynn ;

Shih, Alan ;

Stein, Eytan M. ;

Roshal, Mikhail ;

David, Muriel D. ;

Marteyn, Benoit ;

Farnoud, Noushin Rahnamay ;

de Botton, Stephane ;

Bernard, Olivier A. ;

Wu, Bin ;

Yen, Katharine E. ;

Tallman, Martin S. ;

Papaemmanuil, Elli ;

Penard-Lacronique, Virginie ;

Thakurta, Anjan ;

Vyas, Paresh ;

Levine, Ross L. .

BLOOD, 2017, 130 (06) :732-741

[5] IDH1 and IDH2 mutations in pediatric acute leukemia [J].

Andersson, A. K. ;

Miller, D. W. ;

Lynch, J. A. ;

Lemoff, A. S. ;

Cai, Z. ;

Pounds, S. B. ;

Radtke, I. ;

Yan, B. ;

Schuetz, J. D. ;

Rubnitz, J. E. ;

Ribeiro, R. C. ;

Raimondi, S. C. ;

Zhang, J. ;

Mullighan, C. G. ;

Shurtleff, S. A. ;

Schulman, B. A. ;

Downing, J. R. .

LEUKEMIA, 2011, 25 (10) :1570-1577

[6]

[Anonymous], P AM SOC HEM ANN M 2

[7]

[Anonymous], P AM SOC HEM ANN M 2

[8]

[Anonymous], P AM SOC HEM ANN M 2

[9]

[Anonymous], P AM SOC HEM ANN M 2

[10] Evidence for Clinical Differentiation and Differentiation Syndrome in Patients With Acute Myeloid Leukemia and IDH1 Mutations Treated With the Targeted Mutant IDH1 Inhibitor, AG-120 [J].

Birendra, K. C. ;

DiNardo, Courtney D. .

CLINICAL LYMPHOMA MYELOMA & LEUKEMIA, 2016, 16 (08) :460-465

← 1 2 3 4 5 6 7 →