The Myelodysplastic Syndromes and Myeloproliferative Disorders

Extract

The myelodysplastic syndromes (MDS) and the myeloproliferative disorders (MPD) are a diverse group of hematologic diseases characterized by deregulation of the CD34⁺ hematopoietic stem cell, and with a propensity to transform to acute myeloblastic leukemia (AML). As is true for the acute leukemias, there has been intense interest in determining the molecular mechanisms underlying the cellular deregulation, and the development of more targeted therapies based on unique molecular phenotypes.

In 1997, the Clinical Advisory Committee of the World Health Organization (WHO) published a revised classification of neoplastic diseases of the hematopoietic and lymphoid tissues. This new WHO classification system incorporated morphologic, biologic, and genetic information into a working nomenclature that had clinical relevance, and replaced the previous French-American-British (FAB) classification which was predominantly a morphologic classification system.¹ This paper will not attempt a comprehensive discussion of the WHO classification system, but will summarize the significant changes, and then discuss selected aspects of the MDS/MPDs presented at the 45th Annual Meeting of the American Society of Hematology.

The WHO classification of the chronic myeloproliferative diseases lists seven disease entities (Table 1). The major changes from the FAB classification are:

1. Only the Philadelphia chromosome+ cases (or those with the BCR/ABL fusion gene) are called chronic myelocytic leukemia (CML) by the WHO system. The Phcases, which show myelodysplastic signs, and are known to have significantly worse prognosis, are called atypical CML (aCML), and belong to the newly created myelodysplastic/myeloproliferative group.

2. There are two newly recognized entities which were not included in the FAB…

ABBREVIATIONS: AML = acute myelocytic leukemia; APL = acute promyelocytic leukemia; CML = chronic myelocytic leukemia; CMML = chronic myelomonocytic leukemia; CMPD = chronic myeloproliferative disorders; ET = essential thrombocythemia; FAB = French American British; FDA = Food and Drug Administration; HDAC = histone deacetylase; HDACi = HDAC inhibitor; HSCT = hematopoietic stem cell transplantation; HU = hydroxyurea; IMF = idiopathic myelofibrosis; MDS = myelodysplastic syndromes; PDGF = platelet derived growth factor; PRV-1 = polycythemia rubra vera-1; PV = polycythemia vera; RA = refractory anemia; RARS = refractory anemia with ringed sideroblasts; RCMD = refractory cytopenia with multilineage dysplasia; RAEB = refractory anemia with excess blasts; RCMD-RS = RCMD with ringed sideroblasts; TGF-β = transforming growth factor beta; TNF-α = tumor necrosis factor alpha; TPO = thrombopoietin; VEGF = vascular endothelial growth factor; VEGFR = vascular endothelial growth factor receptor; WHO = World Health Organization.