Research Papers:

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

Andrés E. Quesada _, Zhihong Hu, Mark J. Routbort, Keyur P. Patel, Rajyalakshmi Luthra, Sanam Loghavi, Zhuang Zuo, C. Cameron Yin, Rashmi Kanagal-Shamanna, Sa A. Wang, Jeffrey L. Jorgensen, L. Jeffrey Medeiros and Chi Young Ok

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Oncotarget. 2018; 9:8441-8449. https://doi.org/10.18632/oncotarget.23878

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Andrés E. Quesada1, Zhihong Hu1, Mark J. Routbort1, Keyur P. Patel1, Rajyalakshmi Luthra1, Sanam Loghavi1, Zhuang Zuo1, C. Cameron Yin1, Rashmi Kanagal-Shamanna1, Sa A. Wang1, Jeffrey L. Jorgensen1, L. Jeffrey Medeiros1 and Chi Young Ok1

1Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Correspondence to:

Chi Young Ok, email: [email protected]

Keywords: mixed phenotype; leukemia; mutations; sequencing

Received: July 29, 2017     Accepted: November 05, 2017     Published: January 03, 2018


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.

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