Diagnostic and Prognostic Significance of Cytogenetics in Adult Primary Myelodysplastic Syndromes

Abstract

Cytogenetic analysis has proven to be a mandatory part of the diagnosis of myelodysplastic syndromes (MDS) as well as a major indicator for predicting clinical course and outcome. This review concentrates on the cytogenetic classifications, the incidence and types of chromosome defects and the prognostic significance of the karyotype in adult primary MDS. Two cytogenetic classifications are currently used: one is based on the karyotype complexity (normal, single, double or complex defects), the other on clonal status (all metaphases normal, abnormal or admixture of normal and abnormal clones). Chromosome abnormalities are of both numerical and structural types. Aside from the 5q-syndrome, no specific clinico-cytogenetic entity has been reported. However, several distinct clinical and cellular features have been identified that correlate with the presence of specific chromosome defects such as inv(3)/t(3;3), +6, t(5;12), del(17p) and del(20q). The presence of complex defects is associated with reduced survival and a high risk of leukemic transformation. Among single defects, specific abnormalities may define distinct prognostic groups. Patients with del(5q) as a sole chromosome defect and a refractory anemia without excess of blasts have a favourable prognosis. For patients with trisomy 8 or monosomy 7 there may be distinct types of clinical evolution. Most patients with the 3q21q26 syndrome have a short survival. The presence of two chromosome defects may constitute an independent cytogenetic entity probably associated with relative poor prognosis. Karyotypic evolution generally represents a poor risk factor. The combination of cytogenetics with clinical and hematological features has proven to provide for a better prediction of patients' survival, leukemic transformation and response to treatment. Several scoring systems have been developed. They have to be improved by the study of new patients according to strict clinical and cytogenetic criteria and by the addition of newly recognized prognostic indicators such as histopathological features and molecular genetic mutations.

Incidence and prognostic significance of karyotype abnormalities in de novo primary myelodysplastic syndromes: a study on 331 patients from a single institution

“…[3][4][5][6][7][8][9][10][11][12][13][14][15][18][19][20][21][22][23][24][25][26] Chromosome defects were more common in RAEB and RAEB-t than in RARS and RA. Deletions or gains of entire chromosomes had an incidence of 60.4% and translocations of only 1.8%.…”

“…Chromosome abnormalities are detected in about 40-70% of de novo MDS, confirm the clonality of the disorder, and, except for the 5q-syndromes, are not specific for any FAB subtype. [3][4][5] In addition, in the 1980s, various studies have demonstrated the prognostic relevance of chromosome abnormalities. [6][7][8][9] Following the FAB classification, five scoring systems based on clinical and laboratory findings have been developed in order to better define overall survival (OS) and the time to MDS/AML progression (PFI) in MDS patients.…”

Clonal Karyotype Evolution Involving Ring Chromosome 1 with Myelodysplastic Syndrome Subtype RAEB-t Progressing into Acute Leukemia

“…We describe a case of MDS and secondary AML in a relatively young man with a favorable clinical course, although the cytogenetic fi ndings of a ring chromosome and a complex aberrant karyotype would normally indicate a rather poor prognosis [1,2,4,36,37] . Also, there was rapid progression to a secondary acute leukemia, which is often harder to treat than the primary leukemia and has a very short survival time.…”

“…Independent of FAB types cytogenetics contributes important diagnostic and prognostic data in AML and MDS which give clues for therapeutic decisions [17,36,37] . Ring chromosomes are rare cytogenetic fi ndings in MDS.…”

Myelodysplastic syndromes: prognostic significance of multilineage dysplasia in patients with refractory anemia or refractory anemia with ringed sideroblasts

“…[6][7][8][9] Moreover, the authors discuss that multilineage dysplastic features correlate with severe cytogenetic abnormalities. To our knowledge, no paper has been published supporting this hypothesis in MDS.…”