The evolving nosology of myeloid neoplasms: the semi-centennial of the 1976 French-American-British classification

The year 2026 marks the semi-centennial of the first iteration of the classification schema for myeloid neoplasms, namely the 1976 French-American-British (FAB) classification created by John M. Bennett and colleagues. The FAB classification of acute leukemia formed the biological framework of our current understanding of myeloid neoplasia. Reflecting from this historical lens, we have seen remarkable advances in diagnostics, prognostication, and therapeutics over the decades. Concerted efforts from various consensus groups have paved the way for these advances. Herein, we perform a historical analysis of the evolution of the nosology of myeloid neoplasms over the past 50 years, beginning with the landmark 1976 FAB classification. We discuss how the new nosology of myeloid neoplasms has been inspired by the widespread availability of next-generation sequencing technology as a critical adjunct to classical morphological assessment. We discuss evidence in support of a conceptual framework for categorizing myeloid neoplasms based on ontogeny, beginning from clonal hematopoiesis of indeterminate potential (CHIP). We review the foundational definitions of CHIP, including parallels with Darwinism at the cellular level, and the relevance of incorporation of precursor conditions into the most recent disease classification of myeloid neoplasms. We shed light onto patient-focused practical implications of classification schema, with emphasis on mutation-adapted therapeutic strategies. Finally, we discuss how emerging techniques such as single-cell sequencing and multi-omics may integrate into future revisions.