Genetic Testing in the Diagnosis and Biology of Acute Leukemia

2017 Society for Hematopathology/European Association for Haematopathology Workshop Report

Marian H. Harris, MD, PhD; David R. Czuchlewski, MD; Daniel A. Arber, MD; Magdalena Czader, MD, PhD


Am J Clin Pathol. 2019;152(3):322-346. 

In This Article

Abstract and Introduction


Objectives: The 2017 Workshop of the Society for Hematopathology/European Association for Haematopathology examined the role of molecular genetics in the diagnosis and biology of acute leukemia.

Methods: Acute leukemias were reviewed in two sessions: "Genetic Testing in Diagnosis of Acute Leukemias" (53 cases) and "Genetics Revealing the Biology of Acute Leukemias" (41 cases).

Results: Cases included acute lymphoblastic leukemia, acute myeloid leukemia, and acute leukemia of ambiguous lineage. Many cases demonstrated genetic alterations of known diagnostic, prognostic, and/or therapeutic significance, while others exhibited alterations that illuminated disease biology. The workshop highlighted the complexity of acute leukemia diagnosis and follow-up, while illustrating advantages and pitfalls of molecular genetic testing.

Conclusions: Our understanding of the molecular genetics of acute leukemias continues to grow rapidly. Awareness of the potential complexity of genetic architecture and environment is critical and emphasizes the importance of integrating clinical information with morphologic, immunophenotypic, and molecular genetic evaluation.


Acute leukemias are a diverse group of diseases. The revised World Health Organization (WHO) classification (fourth edition) describes three major categories of acute leukemia: acute lymphoblastic leukemia (ALL, derived from B-, T-, or, rarely, natural killer-cell precursors), acute myeloid leukemia (AML, derived from myeloid precursors including monocytic/myelomonocytic, granulocytic, erythroid, or megakaryocytic precursors), and acute leukemia of ambiguous lineage (ALAL), which includes acute undifferentiated leukemia (AUL, without lineage defining markers), and mixed phenotype acute leukemia (MPAL, with defining markers from multiple lineages).[1]

Multiple subcategories are defined based on immunophenotypic, cytogenetic, and, more recently, molecular genetic findings. For a complete diagnostic, prognostic, and therapeutic evaluation, it is necessary to test for the recognized WHO subtypes of AML, ALL, and MPAL, as well as to perform mutational analysis as recommended by the recent College of American Pathologists/American Society for Hematology (CAP/ASH) guidelines.[2] Thus most patients need a combination of karyotype, fluorescence in situ hybridization (FISH; in some cases), and a limited amount of sequencing. This information is combined with clinical, morphologic, and immunophenotypic findings to yield the diagnosis.

In the 2017 Workshop of the Society for Hematopathology/European Association for Haematopathology, Drs Arber and Harris chaired session 3, "Genetic Testing in Diagnosis of Acute Leukemias," while Drs Czader and Czuchlewski chaired session 7, "Genetics Revealing the Biology of Acute Leukemias." A total of 94 cases of acute leukemias were submitted to the workshop. Session 3 reviewed how cytogenetics and molecular genetic testing aid in the diagnosis of acute leukemias, while session 7 presented how molecular genetic findings can elucidate the biology or pathogenesis of acute leukemias, and showed examples of cases with unexpected or unusual genetic findings. The proceedings of sessions 3 and 7 are combined in this review article.