Complex karyotype



cytopenia with multi-lineage dysplasia 50%; and refractory anemia with excess blasts type I & II 30-50%.32 Cytogenentic abnormalities do not correlate with WHO subtypes, except for the 5q- syndrome, which represents a separate entity, and isodicentric X chromosome associated with ring sideroblasts.31


Loss of chromosome 5 or interstitial deletion of its long arm is one of the most common chromosomal abnormalities described in primary and therapy-related MDS (see Table 38.2). This abnormality is associated with previous exposure to carcinogens, including benzene, alkylating agents, and radiation.33 This -5/del(5q) abnormality is distinguished from the 5q-syndrome. The 5q- syndrome is associated with a macrocytic anemia and often thrombocytosis. It occurs more commonly in upper middle age females, and carries the best prognosis of MDS subtypes. The deletion in the 5q- syndrome breakpoint, which involves band 5q33, contains a different myeloid tumor-suppressor gene from the 5q31 band that is commonly involved in -5/del (5q).31

Chromosomal abnormalities are described in 40-70% of all MDS cases.30 Chromosomal abnormalities usually consist of an unbalanced loss, deletion, or translocation. It may be surprising to find a normal karyotype in 30-60% of a clonal disease; however, this could be explained by technical failures, as well as karyotypic evolution over time. A normal karyotype does, however, carry a better prognosis, similar to the 5q- syndrome, 20q-, or loss of chromosome Y. A complex karyotype is defined as the presence of three or more different cytogenetic abnormalities. It occurs in 10-20% of primary MDS and in up to 90% of therapy-related MDS. Table 38.2 lists the most common chromosomal abnormalities in primary and therapy related MDS.31 More cytogenetic abnormalities occur in high risk MDS and therapy related MDS. The reported frequency of cytogenetic abnormalities under the new WHO classification are: refractory anemia 25%; refractory anemia with ring sideroblasts 10%; refractory


Monosomy 7 or deletion of the long arm of chromosome 7 is well described in therapy-related MDS and primary MDS (see Table 38.2). The breakpoint 7q22 is more commonly associated with MDS cases. A monosomy 7 syndrome entity is described in the pediatric literature, and is common in juvenile myelomonocytic leukemia (JMML). Interestingly, -7/del(7q) is the most common abnormality described in patients with hereditary predispositions to MDS, such as Fanconi anemia.3134

Loss of 7q is associated with AML1 gene mutations. Monosomy 7 or deletion of the long arm of chromosome 7 is associated with a poor outcome in children and adults.

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