Prognosis of Myelodysplastic Syndromes

Abstract

The myelodysplastic syndromes (MDS) are a very complex group of hematopoietic disorders. The degree of complexity relates not only to the intrinsic pathobiological characteristics of the disease, but also to the group of patients whom it affects most frequently: older individuals or those who have been exposed to prior forms of chemotherapy. It is therefore crucial to develop clinical tools to predict with a certain degree of precision the prognosis and outcome for patients with specific subtypes of MDS in specific clinical situations. At the present time, patients with MDS are diagnosed using a set of well-established histopathological criteria. Prognosis is established using classifications that include morphological features, percentage of blasts, and clinical and molecular characteristics such as peripheral cytopenias and cytogenetics. The International Prognostic Scoring System (IPSS) is a classic example of this type of classification. Over the last 5 years, there has been an intense effort to develop new prognostic systems for MDS, and new molecular alterations with potential prognostic value have been discovered. Over the same period of time, several new therapeutic interventions have been developed for patients with MDS. Biomarkers of response to these agents, in particular for the hypomethylating agents, are needed to predict clinical benefit. This review summarizes current prognostic models of MDS and new molecular alterations with potential prognostic potential.

Protein Kinase R as Mediator of the Effects of Interferon (IFN) γ and Tumor Necrosis Factor (TNF) α on Normal and Dysplastic Hematopoiesis

“…Deregulation in the production of myelosuppressive cytokines promotes development of various pathophysiological states, including marrow failure and myelodysplastic syndromes (MDS) (7,45). MDS includes a heterogeneous group of diseases characterized by dysplastic hematopoiesis (46,47), in which immune deregulation appears to play important pathobiologic roles. Recent work has provided evidence for expansion of abnormal auto reactive CD8ϩ T lymphocytes in the bone marrow of patient with low to intermediate risk MDS, suggesting a mechanism for the overproduction of myelosuppressive cytokines that target hematopoietic precursors in MDS (47)(48)(49)(50).…”

Epigenetics in Cancer: The Myelodysplastic Syndrome as a Model to Study Epigenetic Alterations as Diagnostic and Prognostic Biomarkers

“…However, despite its importance, this system has some limitations like the risk groups in relation to karyotype. In some studies, trisomy 8, for example, is often associated with disease progression (Fernandez et al, 2000;Garcia-Manero, 2010;Solé et al, 2000). However, the IPSS classifies this chromosomal alteration with intermediate prognosis.…”

Molecular genetic methods in the diagnosis of myelodysplastic syndromes. A review

“…However, there is no clear molecular alteration to explain the lenalidomide response. Research of predictive biomarkers for the response to hypomethylating agents is one of the most important in the MDS field, however no presumed predictive association between specific methylation patterns and treatment response was found 1,2 . Genetic evolution of MDS is a dynamic process characterized by multiple cycles of acquisition of genetic abnormalities and subsequent clonal selection.…”

“…MDS are clinically associated with ineffective hemopoiesis, peripheral blood cytopenia and increased risk of progression to acute myeloid leukemia (AML) in approximately one-third of patients. MDS are most frequently diagnosed in elderly individuals and have highly variable clinical course and prognosis 1 . In many patients, MDS are asymptomatic and appear as an abnormality on a routine blood cell count.…”