What are the MPAL (Megakaryoblastic Acute Leukemia) criteria?

From the Guidelines

The MPAL criteria are used to diagnose a rare type of acute leukemia that shows features of both myeloid and lymphoid lineages, with myeloid lineage established by the presence of myeloperoxidase (MPO) or monocytic differentiation, T-lineage by cytoplasmic CD3 expression, and B-lineage by strong CD19 expression with at least one of: CD79a, cytoplasmic CD22, or CD10, as defined by the World Health Organization (WHO) classification 1.

Key Points

• The diagnosis of MPAL requires comprehensive flow cytometry analysis of bone marrow or peripheral blood samples.
• MPAL can be further classified as B/myeloid, T/myeloid, B/T, or trilineage (B/T/myeloid).
• The classification is important because MPAL generally has a poorer prognosis than single-lineage acute leukemias and may require different treatment approaches, often incorporating elements of both acute lymphoblastic leukemia and acute myeloid leukemia therapy regimens.

Diagnostic Criteria

• Myeloid lineage: MPO by flow cytometry, immunohistochemistry, or cytochemistry, or monocytic differentiation (at least 2 of the following: nonspecific esterase cytochemistry, CD11c, CD14, CD64, lysozyme) 1.
• T-lineage: cytoplasmic CD3 expression.
• B-lineage: strong CD19 expression with at least one of: CD79a, cytoplasmic CD22, or CD10.

Clinical Significance

• MPAL has a poorer prognosis than single-lineage acute leukemias.
• Treatment approaches may incorporate elements of both acute lymphoblastic leukemia and acute myeloid leukemia therapy regimens.
• Accurate diagnosis and classification are crucial for optimal treatment and management of MPAL, as highlighted in the 2017 ELN recommendations 1 and the 2008 WHO classification 1.

From the Research

Mpal Criteria

• The World Health Organization (WHO) classification is used to diagnose Mixed Phenotype Acute Leukemia (MPAL) 2, 3, 4, 5, 6
• MPAL is characterized by the presence of multilineage immunophenotypic markers and may have a shared B/T/myeloid phenotype 2
• The diagnosis of MPAL is based on the expression of specific markers, including myeloperoxidase, CD19, and cytoplasmic CD3 2
• The WHO 2008 and 2016 classifications define three categories of MPAL: associated with t(9;22)/BCR-ABL1 fusion gene, associated with KMT2A (mixed lineage leukemia) rearrangements, and nonotherwise specified 5
• Flow cytometry and immunohistochemistry are used to assign acute leukemia to the MPAL category 5

Diagnostic Criteria

• MPAL is diagnosed when blasts in peripheral blood and/or bone marrow have antigens of more than one lineage or a mosaic of blasts belonging to more than one lineage 3
• The European Group for the Immunological Classification of Leukaemias Criteria and WHO 2008/2016 guidelines are used for lineage assignment 3
• Multiparametric flow cytometry is essential for the accurate diagnosis of MPAL 3, 5

Classification

• MPAL can be classified into two types: "bilineal" and "biphenotypic" 4, 5
• Bilineal MPAL is characterized by the coexistence of two blast populations of different lineage, while biphenotypic MPAL coexpresses markers of more than one lineage in a homogenous blast population 5