Virginia M Klimek1, Nancy J Tray. 1. aDepartment of Medicine, Leukemia Service bHospital Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, USA.
Abstract
PURPOSE OF REVIEW: Therapy-related myeloid neoplasms (tMN) are increasingly recognized and studied diseases which have traditionally been defined clinically. With advances in methods used to study the genetics of aging and myeloid disease biology, novel insights are emerging which are expected to improve our understanding of the genetics and pathogenesis of tMN. RECENT FINDINGS: Clinical outcomes in tMN and de novo MDS/AML appear to be largely determined by genetics, and data are emerging to show how DNA mutations may enhance tMN risk stratification. The discovery of skewed hematopoieses and mutations in healthy older adults suggests an alternate predisposition mechanism for the genesis of tMN. Patients with tMN do respond to standard therapy and can benefit from allogeneic transplant in a manner similar to their genetically matched de novo counterpart. SUMMARY: De novo MDS/AML and tMN have shared genetic features, and tMN clinical outcomes may depend more on the genetics at presentation than the clinical history of an antecedent malignancy. Acquired somatic mutations in genes such as TP53 and myeloid skewing with associated mutations in cancer-free older adults may predispose such individuals to tMN under the influence of myelosuppressive therapy, and this may be a route to the development of a subset of tMN.
PURPOSE OF REVIEW: Therapy-related myeloid neoplasms (tMN) are increasingly recognized and studied diseases which have traditionally been defined clinically. With advances in methods used to study the genetics of aging and myeloid disease biology, novel insights are emerging which are expected to improve our understanding of the genetics and pathogenesis of tMN. RECENT FINDINGS: Clinical outcomes in tMN and de novo MDS/AML appear to be largely determined by genetics, and data are emerging to show how DNA mutations may enhance tMN risk stratification. The discovery of skewed hematopoieses and mutations in healthy older adults suggests an alternate predisposition mechanism for the genesis of tMN. Patients with tMN do respond to standard therapy and can benefit from allogeneic transplant in a manner similar to their genetically matched de novo counterpart. SUMMARY: De novo MDS/AML and tMN have shared genetic features, and tMN clinical outcomes may depend more on the genetics at presentation than the clinical history of an antecedent malignancy. Acquired somatic mutations in genes such as TP53 and myeloid skewing with associated mutations in cancer-free older adults may predispose such individuals to tMN under the influence of myelosuppressive therapy, and this may be a route to the development of a subset of tMN.
Authors: R J Molenaar; C Pleyer; T Radivoyevitch; S Sidana; A Godley; A S Advani; A T Gerds; H E Carraway; M Kalaycio; A Nazha; D J Adelstein; C Nasr; D Angelini; J P Maciejewski; N Majhail; M A Sekeres; S Mukherjee Journal: Leukemia Date: 2017-11-06 Impact factor: 11.528
Authors: Remco J Molenaar; Surbhi Sidana; Tomas Radivoyevitch; Anjali S Advani; Aaron T Gerds; Hetty E Carraway; Dana Angelini; Matt Kalaycio; Aziz Nazha; David J Adelstein; Christian Nasr; Jaroslaw P Maciejewski; Navneet S Majhail; Mikkael A Sekeres; Sudipto Mukherjee Journal: J Clin Oncol Date: 2017-12-18 Impact factor: 50.717
Authors: María Del Carmen Vicente-Ayuso; María García-Roa; Ataúlfo González-Fernández; Ana María Álvarez-Carmona; Celina Benavente-Cuesta; Marta Mateo-Morales; Cristina Pérez-López; Ascensión Peña-Cortijo; Marta Polo Zarzuela; Laura Gutiérrez; Rafael Martínez-Martínez Journal: Hematol Rep Date: 2017-09-27