Myelodysplastic syndromes (MDS) constitute a heterogeneous group of clonal hematopoietic stem cell disorders marked by ineffective blood cell production and peripheral cytopenias.
Characterized by dysplastic changes within the bones marrow, MDS frequently leads to anemia, neutropenia, thrombocytopenia, and a heightened risk of progression to acute myeloid leukemia (AML).
Clinical Manifestations and Hematologic Abnormalities
Patients with MDS often present with symptoms directly linked to cytopenias. Anemia is the most common manifestation and may cause fatigue, dyspnea, and pallor. Thrombocytopenia can manifest as easy bruising, petechiae, mucosal bleeding, or prolonged hemorrhage from minor injuries. Neutropenia predisposes individuals to recurrent infections, which constitute a major cause of morbidity and mortality.
Pathophysiology and Molecular Characteristics
At the core of MDS pathogenesis lies somatic mutations within hematopoietic stem cells resulting in clonal expansion. Genetic abnormalities, including chromosomal deletions (5q-, 7q-), complex karyotypes, and mutations in genes like TP53 and RUNX1, contribute significantly to disease severity and evolution.
These mutations impair normal hematopoiesis causing ineffective differentiation and cellular apoptosis, culminating in peripheral cytopenias despite a hypercellular marrow in many cases.
Diagnostic Considerations and Risk Stratification
Accurate diagnosis necessitates morphological confirmation of dysplasia in bones marrow aspirates and biopsies supported by cytogenetic and molecular analyses. Peripheral blood cytopenias in conjunction with characteristic marrow abnormalities confirm MDS in the absence of other causes.
The International Prognostic Scoring System – Revised (IPSS-R) and newer molecularly informed IPSS-M models allow risk stratification by incorporating blast percentage, cytogenetics, and genetic mutations, guiding prognosis and treatment decisions. This stratification distinguishes lower-risk patients, who may have prolonged survival and may not require immediate intervention, from higher-risk groups with rapid progression to AML and poorer outcomes.
Complications and Prognosis
Infections due to neutropenia and hemorrhagic complications secondary to thrombocytopenia are principal causes of morbidity. Iron overload from repeated transfusions contributes to multi-dysfunction impacting cardiac and hepatic function. Transformation to acute myeloid leukemia represents a critical turning point associated with poor prognosis.
Prognostic factors for survival include age, cytogenetic abnormalities, marrow blast count, and comorbid medical conditions. Recent studies highlight that patients exhibiting complex karyotypes or mutations in TP53 tend to have inferior outcomes and shorter survival durations.
Current Perspectives and Therapeutic Approaches
Management is increasingly tailored to disease risk and patient factors, ranging from supportive care to hematopoietic stem cell transplantation—the only curative therapy. Hypomethylating agents and novel targeted therapies have shown promise in modifying disease course and improving quality of life in higher-risk patients.
Dr. Mikkael A. Sekeres, a leading expert, emphasized, "Recognition of the genetic landscape and functional heterogeneity in MDS enables clinicians to apply precision medicine, aligning treatment strategies with individual risk profiles to improve survival."
Similarly, Dr. Guillermo Garcia - Manero stated, "Advances in molecular diagnostics and prognostic scoring have transformed the approach to MDS, allowing earlier intervention and more rational use of emerging therapies." Their perspectives underscore the importance of integrating comprehensive diagnostic tools with personalized treatment paradigms.
Myelodysplastic syndromes encompass a complex and diverse group of hematopoietic disorders characterized by ineffective blood cell production and risk of malignant transformation. Accurate diagnosis and modern prognostic scoring inform individualized management, balancing supportive care with disease-modifying therapies.
Continued research into molecular pathogenesis and therapeutic innovations holds promise for improved outcomes in this challenging hematologic neoplasm.
