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Updated: Jun 18, 2026

Assessment of the Metabolic Profile of Primary Leukemia Cells
Published on: November 21, 2018
Diagnosis of biphenotypic acute leukemia: a paradigmatic approach
Xianfeng Frank Zhao1, Ivana Gojo, Teresa York
1Department of Pathology, University of Maryland School of Medicine, Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA. xzhao@umm.edu
Insights
Biphenotypic acute leukemia (BAL) is rare. A new approach reclassifies most BAL cases as acute lymphoblastic leukemia (ALL), improving diagnostic accuracy for this complex blood cancer.
Area of Science:
- Hematology
- Immunophenotyping
- Oncology
Background:
- Biphenotypic acute leukemia (BAL) involves a single blast population expressing markers from two lineages, posing diagnostic challenges.
- Existing classification systems like EGIL and WHO have limitations in accurately defining and managing BAL.
- Optimal diagnostic criteria are needed for precise patient management and treatment stratification.
Purpose of the Study:
- To propose and validate a novel approach for defining BAL.
- To re-evaluate existing BAL classifications using updated immunologic and cytogenetic data.
- To improve the diagnostic accuracy and clinical utility of BAL classification.
Main Methods:
- Development of a new diagnostic paradigm for BAL based on recent clinical and scientific advancements.
- Application of the new criteria to a cohort of 8 "BAL" cases within 742 new acute leukemias.
- Comparative analysis with previously reported BAL cases from other institutions.
Main Results:
- The proposed new criteria reclassified 6 out of 8 "BAL" cases as acute lymphoblastic leukemia (ALL).
- Only 2 cases remained classified as BAL under the new diagnostic framework.
- The approach demonstrated consistency with analyses of previously published BAL cases.
Conclusions:
- The proposed new approach offers a more refined method for defining BAL.
- This reclassification highlights potential overdiagnosis of BAL with current systems.
- The findings support a revised understanding of BAL, aiding in better clinical management.
Abstract:
Biphenotypic acute leukemia (BAL), or acute leukemia with a single population of blasts coexpressing markers of two different lineages, is a rare clinical entity. To define BAL, a scoring system was proposed by the European Group of Immunological Markers for Leukemias (EGIL) in 1995. However, increasing evidence suggests that this system has limitations, as acknowledged by the 2008 World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues. Although substantially improved in relation to the EGIL, the new WHO Classification is still not optimal for guiding the clinical management of patients with BAL. We propose a new paradigmatic approach to defining BAL based on recent clinical studies of BAL and advances in immunologic marker definition and cytogenetics, and applied our new approach to 8 cases of "BAL" among a cohort of 742 new acute leukemias in our Cancer Center. By our new criteria, 6 cases were reclassified as acute lymphoblastic leukemia (ALL), while only 2 were still classified as BAL. Our approach is also supported by analyses of the BAL cases previously reported by other institutions.

