Acute Leukemias with Complex Karyotype Show a Similarly Poor Outcome Independent of Mixed, Myeloid or Lymphoblastic Immunophenotype: A Study from the Bone Marrow Pathology Group

Authors

Timothy Kirtek, Department of Pathology, UT Southwestern Medical Center, USA.
Weina Chen, Department of Pathology, UT Southwestern Medical Center, USA.
Dorottya Laczko, Department of Pathology, Perelman School of Medicine, Hospital of the University of Pennsylvania, USA.
Adam Bagg, Department of Pathology, University of Pennsylvania, USA.
Prasad Koduru, Department of Pathology, UT Southwestern Medical Center, USA.
Kathryn Foucar, Department of Pathology, University of New Mexico, USA.
Elise Venable, Department of Pathology, University of New Mexico, USA.
Meredith Nichols, Department of Pathology, Cleveland Clinic Tomsich Pathology & Laboratory Medicine Institute, USA.
Heesun J. Rogers, Department of Pathology, Cleveland Clinic Tomsich Pathology & Laboratory Medicine Institute, USA.
Wayne Tam, Department of Pathology, Weill Cornell Medicine, USA.
Attilio Orazi, Department of Pathology, Texas Tech University Health Science Center, USA.
Eric D. Hsi, Department of Pathology, Wake Forest Baptist Health, USA.
Robert P. Hasserjian, Department of Pathology, Massachusetts General Hospital, Harvard Medical School, USA.
Sa A. Wang, Department of Pathology, UT MD Anderson Cancer Center, USA.
Daniel A. Arber, Department of Pathology, University of Chicago, USA.
Olga K. Weinberg, Department of Pathology, UT Southwestern Medical Center, USA.Follow

Document Type

Article

Publication Date

7-1-2023

Abstract

Mixed phenotype acute leukemia (MPAL) is a heterogenous group of acute leukemias characterized by leukemic blasts that express markers of multiple lineages. The revised 4th edition WHO classification of MPAL excludes AML with myelodysplasia related changes (AML-MRC), including those with complex karyotype (CK), from a diagnosis of MPAL. Abnormal karyotype is frequent in MPAL with the reported rate of CK in MPAL ranging from 19% to 32%. Due its rarity, the clinical and genetic features of MPAL with CK remain poorly characterized. This study aims to further characterize the genetic features of MPAL with CK in comparison to cases of AML and ALL with CK. Cases of de novo MPAL, AML, and B- and T-ALL patients with CK were collected from 8 member institutions of the Bone Marrow Pathology Group. We found no significant difference in overall survival between MPAL with CK compared to AML and ALL with CK. AML with CK was more strongly associated with TP53 mutations, however the presence of TP53 mutations conferred a worse prognosis regardless of lineage. ALL with CK seems to show increased IKZF1 mutation rates which is known to confer a worse prognosis in ALL. Additionally, MPAL with CK showed similarly poor outcomes regardless of whether a lymphoid or myeloid chemotherapy regimen is chosen. Our results suggest that acute leukemias with complex karyotype show a similarly poor outcome regardless of lineage differentiation and that mutation in TP53 confers a poor prognosis in all lineages. Our results support the exclusion of immunophenotypic MPAL with CK from MPAL and appear to confirm the approach proposed in the revised 4th edition WHO to include them as AML with myelodysplasia-related changes and similar myelodysplasia-related AML categories of newer classifications.

Recommended Citation

Kirtek T, Chen W, Laczko D, Bagg A, Koduru P, Foucar K, Venable E, Nichols M, Rogers HJ, Tam W, Orazi A, Hsi ED, Hasserjian RP, Wang SA, Arber DA, Weinberg OK. Acute leukemias with complex karyotype show a similarly poor outcome independent of mixed, myeloid or lymphoblastic immunophenotype: A study from the Bone Marrow Pathology Group. Leuk Res. 2023 Jul;130:107309. doi: 10.1016/j.leukres.2023.107309. Epub 2023 May 10. PMID: 37210875.