PURPOSE OF REVIEW: Acute myeloid leukemia (AML) is a highly heterogeneous disorder being composed of various genetically defined subtypes. In recent years, molecular research provided the basis for a more differentiated characterization of AML patients, for example, of the large subgroup with normal karyotypes. This review summarizes the current status of molecular diagnostics in AML and refers to the diagnostic techniques being most suitable for the individual markers. RECENT FINDINGS: A molecular data set based on mutations of the NPM1, FLT3, and CEBPA genes and the MLL-PTD provides a prognostically relevant risk stratification that can support the decision pro or con an allogeneic hematopoietic stem cell transplantation in first remission. The panel of known molecular markers is continuously increasing, for example, considering the recently described TET2 and IDH1 mutations. The introduction of next generation sequencing will certainly catalyze the molecular characterization of AML. Monitoring of the minimal residual disease load with quantitative real-time PCR can be performed for NPM1 and MLL-PTD-mutated cases. SUMMARY: Targeted therapy studies with FLT3 inhibitors for patients with FLT3-mutated AML as single agents or combined with chemotherapy illustrate the translation of the molecular techniques into clinical practice already being realized in distinct subgroups of AML.
PURPOSE OF REVIEW: Acute myeloid leukemia (AML) is a highly heterogeneous disorder being composed of various genetically defined subtypes. In recent years, molecular research provided the basis for a more differentiated characterization of AMLpatients, for example, of the large subgroup with normal karyotypes. This review summarizes the current status of molecular diagnostics in AML and refers to the diagnostic techniques being most suitable for the individual markers. RECENT FINDINGS: A molecular data set based on mutations of the NPM1, FLT3, and CEBPA genes and the MLL-PTD provides a prognostically relevant risk stratification that can support the decision pro or con an allogeneic hematopoietic stem cell transplantation in first remission. The panel of known molecular markers is continuously increasing, for example, considering the recently described TET2 and IDH1 mutations. The introduction of next generation sequencing will certainly catalyze the molecular characterization of AML. Monitoring of the minimal residual disease load with quantitative real-time PCR can be performed for NPM1 and MLL-PTD-mutated cases. SUMMARY: Targeted therapy studies with FLT3 inhibitors for patients with FLT3-mutated AML as single agents or combined with chemotherapy illustrate the translation of the molecular techniques into clinical practice already being realized in distinct subgroups of AML.
Authors: John S Welch; Timothy J Ley; Daniel C Link; Christopher A Miller; David E Larson; Daniel C Koboldt; Lukas D Wartman; Tamara L Lamprecht; Fulu Liu; Jun Xia; Cyriac Kandoth; Robert S Fulton; Michael D McLellan; David J Dooling; John W Wallis; Ken Chen; Christopher C Harris; Heather K Schmidt; Joelle M Kalicki-Veizer; Charles Lu; Qunyuan Zhang; Ling Lin; Michelle D O'Laughlin; Joshua F McMichael; Kim D Delehaunty; Lucinda A Fulton; Vincent J Magrini; Sean D McGrath; Ryan T Demeter; Tammi L Vickery; Jasreet Hundal; Lisa L Cook; Gary W Swift; Jerry P Reed; Patricia A Alldredge; Todd N Wylie; Jason R Walker; Mark A Watson; Sharon E Heath; William D Shannon; Nobish Varghese; Rakesh Nagarajan; Jacqueline E Payton; Jack D Baty; Shashikant Kulkarni; Jeffery M Klco; Michael H Tomasson; Peter Westervelt; Matthew J Walter; Timothy A Graubert; John F DiPersio; Li Ding; Elaine R Mardis; Richard K Wilson Journal: Cell Date: 2012-07-20 Impact factor: 41.582
Authors: Timothy J Ley; Christopher Miller; Li Ding; Benjamin J Raphael; Andrew J Mungall; A Gordon Robertson; Katherine Hoadley; Timothy J Triche; Peter W Laird; Jack D Baty; Lucinda L Fulton; Robert Fulton; Sharon E Heath; Joelle Kalicki-Veizer; Cyriac Kandoth; Jeffery M Klco; Daniel C Koboldt; Krishna-Latha Kanchi; Shashikant Kulkarni; Tamara L Lamprecht; David E Larson; Ling Lin; Charles Lu; Michael D McLellan; Joshua F McMichael; Jacqueline Payton; Heather Schmidt; David H Spencer; Michael H Tomasson; John W Wallis; Lukas D Wartman; Mark A Watson; John Welch; Michael C Wendl; Adrian Ally; Miruna Balasundaram; Inanc Birol; Yaron Butterfield; Readman Chiu; Andy Chu; Eric Chuah; Hye-Jung Chun; Richard Corbett; Noreen Dhalla; Ranabir Guin; An He; Carrie Hirst; Martin Hirst; Robert A Holt; Steven Jones; Aly Karsan; Darlene Lee; Haiyan I Li; Marco A Marra; Michael Mayo; Richard A Moore; Karen Mungall; Jeremy Parker; Erin Pleasance; Patrick Plettner; Jacquie Schein; Dominik Stoll; Lucas Swanson; Angela Tam; Nina Thiessen; Richard Varhol; Natasja Wye; Yongjun Zhao; Stacey Gabriel; Gad Getz; Carrie Sougnez; Lihua Zou; Mark D M Leiserson; Fabio Vandin; Hsin-Ta Wu; Frederick Applebaum; Stephen B Baylin; Rehan Akbani; Bradley M Broom; Ken Chen; Thomas C Motter; Khanh Nguyen; John N Weinstein; Nianziang Zhang; Martin L Ferguson; Christopher Adams; Aaron Black; Jay Bowen; Julie Gastier-Foster; Thomas Grossman; Tara Lichtenberg; Lisa Wise; Tanja Davidsen; John A Demchok; Kenna R Mills Shaw; Margi Sheth; Heidi J Sofia; Liming Yang; James R Downing; Greg Eley Journal: N Engl J Med Date: 2013-05-01 Impact factor: 91.245
Authors: Peter Valent; Wolfgang R Sperr; Karl Sotlar; Andreas Reiter; Cem Akin; Jason Gotlib; Hans-Peter Horny; Michel Arock Journal: Expert Rev Hematol Date: 2014-08-28 Impact factor: 2.929