Cytogenetic abnormalities

Clearly, since MDS can progress to AML, all of the cytoge-netic abnormalities found in MDS are also found in AML, although their incidence will differ between MDS and AML. However, certain balanced translocations found in AML are never found in MDS, including the t(15;17), inv(16), t(8;21)

Table 8.1 International Prognostic Scoring System.


Blast % (marrow)












2 or 3



Good (-Y, 5q-, 20q-)


Intermediate (other)


Poor (chromosome 7) or complex (>3 abnormalities)


Total score

Median survival (years)


Low risk



Low to intermediate risk



High to intermediate risk



High risk


*Cytopenia is defined as platelet count <100 x 109/L, hemoglobin <10 g/dl, or neutrophil count <1

.5 x 109/L.

and t(9;11). In MDS the typical abnormalities are partial and complete chromosome loss, most often involving del(5q), -7, -Y and del(20q), and chromosome gain, most often of +8. Such abnormalities are present in approximately 50% of primary MDS and 80% of secondary MDS. These abnormalities provide important prognostic information (as reflected in the IPSS). They also give clues to location of tumor suppressor genes whose deletion is postulated to play an important role in the etiology of MDS.

The del(5q) is the most commonly reported deletion in de novo MDS and is found in 10-15% of all patients (Figure 8.2). Those MDS patients with RA and the del(5q) as the sole abnormality have the 5q- syndrome. This syndrome was described by Van den Berghe and Cassiman in 1974 and has the following hematological features in association with an interstitial deletion of the long arm of chromosome 5: refractory anemia, female preponderance, macrocytosis, normal/ high platelet count, hypolobulated megakaryocytes, and a low transformation rate to AML. There is a clear genotype-phe-notype association and the prognosis of the 5q- syndrome is good (Figure 8.3).

The -7/del(7q) is found in 5-10% of patients with de novo MDS and in approximately 50% of all therapy-related cases. The del(20q) is found in 3-4% of patients with MDS. The commonly deleted regions (CDRs) of the del(5q), del(7q) and del(20q) in MDS have been defined using fluorescence in situ hybridization and molecular mapping. Recently, many of these regions have been significantly narrowed. Gene prediction programs have been used for the complete genomic annotation of the CDRs and this has greatly facilitated the identification of candidate genes. The identification of more than one CDR of the del(5q) and del(7q) suggests the existence of more than one pathogenetically relevant gene.

It remains possible that the deletions involving 5q, 7q and 20q contribute to myeloid malignancy by haploinsufficiency; that is, a dosage affect resulting from the loss of a single al-lele of a gene. Using Cre-loxP based genome engineering, we and others are currently producing chromosomal deletions in mice that mimic those seen in MDS both to define the effect of gene deletion on the development of MDS and for the production of viable models of this disease.

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