Update on the classification of myeloid neoplasms: The 2016 revised World Health Organization classification of hematopoietic and lymphoid neoplasms

Abstract

In recent years, a large body of knowledge regarding the molecular genetics of myeloid malignancies has emerged and molecular findings have become increasingly important not only for diagnosis but also to establish prognosis and treatment of patients with myeloid malignancies. Clinical and pathological findings have been refined in relation to their diagnostic/prognostic value. The integration of all these different parameters represents the backbone of the 2016 revised 4th Edition of the WHO Classification of Tumours of Hematopoietic and Lymphoid Tissues. The current review aims to highlight the main changes between the 2008 WHO Classification and the most recent 2016 revised 4th edition, with regard to the classification of myeloid malignancies. K E Y W O R D S Acute myeloid leukemia, myelodysplastic syndromes, myeloproliferative neoplasms, WHO classification 2 of 9 | SANGIORGIO ANd ORAZI 2.2 | BCR-ABL1 negative myeloproliferative neoplasms | Polycythemia veraMajor changes in the clinical criteria for the diagnosis of polycythemia vera (PV) have been adopted in the revised classification. Hemoglobin (Hb) >18.5 g/dL for men and > 16.5 g/dL for women were the thresholds used to diagnose PV in the 2008 classification. Applying these criteria, many cases of early phase PV were left unrecognized, for example, patients with a red cell mass > 25% of the mean predicted value (thus indicative of increased red cell volume), but with Hb level falling below the stated thresholds. For such cases, the definition of "masked PV" has been introduced. 7,8 Similarly, application of the 2008 criteria can lead to misdiagnose as essential thrombocythemia (ET) cases of early PV presenting with thrombocytosis. 9,10 To address these issues, the revised classification has established Hb > 16.5 for men and > 16.0 for women as the new thresholds for the diagnosis of PV. The newer TA B L E 1 Summary of the major diagnostic changes introduced by the 2016 WHO classification, revised 4th edition

Mesenchymal stromal cells in myeloid malignancies: Immunotherapeutic opportunities

“…These mutations alter cell proliferation, maturation, and differentiation, accumulating abnormal cells and developing malignancies [ 12 , 13 ]. The 2017 update of the World Health Organization (WHO) classification of myeloid malignancies categorizes them into different types, such as AML, MDS, BCR-ABL1/Philadelphia (Ph) positive and negative MPN, and MDS/MPN with hybrid characteristics [ [14] , [15] , [16] ].…”

Mesenchymal Stromal Cells in Myeloid Malignancies: Immunotherapeutic Opportunities

“…These mutations alter cell proliferation, maturation, and differentiation, accumulating abnormal cells and developing malignancies [12,13]. The 2017 update of the World Health Organization (WHO) classification of myeloid malignancies categorizes them into different types, such as AML, MDS, BCR-ABL1/Philadelphia (Ph) positive and negative MPN, and MDS/MPN with hybrid characteristics [14][15][16].…”

Myeloid-Derived Suppressor Cells and Mesenchymal Stem/Stromal Cells in Myeloid Malignancies

“…Malignant transformation can appear at any stage of blood cell development, including HSCs, progenitors, and mature blood cells [104]. According to the 2017 revision of the World Health Organization (WHO) classification of myeloid malignancies, myeloid malignancies include BCR-ABL1/Philadelphia (Ph), positive and negative MPN, MDS, MDS/MPN with mixed features, myeloid and lymphoid neoplasms associated with eosinophilia, gene rearrangements, and AML [105,106]. Next, we analyze the main features of MDSCs and MSCs in myeloid malignancies.…”

“…CML is the BCR-ABL1 oncoprotein-positive MPN characterized by the Philadelphia (Ph) chromosome's presence. The Ph chromosome, a unique biomarker of CML, is a product of reciprocal translocation of the BCR gene on chromosome 22q11.2 and the ABL1 gene located on chromosome 9q34, and about 90-98% of CML patients harbor this mutation [105,177,178]. Furthermore, CML incidence is about 0.7-1.0/100,000 individuals per year; this rate has stabilized in recent years, and the diagnosis is more frequent in the population around 60-70 years old [179].…”

“…Accumulation of CD4+CD25+ forkhead box (FOX)P3+ Tregs, monocytes, macrophages, and MDSCs, and an impaired balance of CD4+/CD8+ have been hypothesized as relevant factors for disease progression and therapeutic resistance [210]. Other atypical MPNs comprise chronic neutrophilic leukemia, chronic eosinophilic leukemia, mastocytosis, and rare clonal disorders characterized by persistent neutrophilia, eosinophilia, or accumulation of mast cells [105].…”