Mixed phenotype acute leukemia contains heterogeneous genetic mutations by next-generation sequencing

// Andrés E. Quesada 1 , Zhihong Hu 1 , Mark J. Routbort 1 , Keyur P. Patel 1 , Rajyalakshmi Luthra 1 , Sanam Loghavi 1 , Zhuang Zuo 1 , C. Cameron Yin 1 , Rashmi Kanagal-Shamanna 1 , Sa A. Wang 1 , Jeffrey L. Jorgensen 1 , L. Jeffrey Medeiros 1 and Chi Young Ok 1 1 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Correspondence to: Chi Young Ok, email: COk@mdanderson.org Keywords: mixed phenotype; leukemia; mutations; sequencing Received: July 29, 2017      Accepted: November 05, 2017      Published: January 03, 2018 ABSTRACT Mixed phenotype acute leukemia (MPAL) is an uncommon manifestation of acute leukemia. The aim of this study is to further characterize the genetic landscape of de novo cases of MPAL that fulfill the 2016 World Health Organization (WHO) classification criteria for this entity. We identified 14 cases examined by next generation sequencing (NGS) using 28 ( n = 10), 53 ( n = 3) or 81 ( n = 1) gene panels: 7 cases with a B-cell/myeloid (B/My) immunophenotype, 6 T-cell/myeloid (T/My) immunophenotype, and 1 B-cell/T-cell (B/T) immunophenotype. A total of 25 distinct mutations were identified in 15 different genes in 9/14 (64%) patients. FLT3 -ITD was the only recurrent mutation in 2 patients. B/My MPAL cases less commonly harbored mutations compared with T/My MPAL cases (43% vs. 100%, p = 0.07). In contrast, B/My MPALs more commonly showed a complex karyotype compared to T/My MPALs (71% vs. 17%, p = 0.1). With NGS and karyotype combined, most (93%) MPAL cases had mutations or cytogenetic abnormalities. With a median follow-up of 12.5 months, there were no significant differences in median overall survival (OS) between patients with B/My or T/My MPAL (17.8 and 6.5 months, respectively, p = 0.81) or between patients with MPAL with versus without gene mutations (6.5 and 13.3 months, respectively, p = 0.86). Our data suggest that the distinguishing cases of MPAL according to immunophenotype has value because the underlying mechanisms of leukemogenesis might differ between B/My and T/My MPAL.