Myelodysplastic Syndrome FISH Probes

Heterozygous, interstitial deletions on chromosome 5q are the most frequently cytogenetic finding in MDS, to the extent that the abnormality characterizes its own MDS subtype known as 5q- syndrome. Haploinsufficiency of key genes in the target region greatly alters hematopoiesis, leading to abnormal blood cell development.

Isolated chromosome trisomy 8 (+8) is one of the most common cytogenetic alterations in MDS, representing 9–11% of de novo MDS with cytogenetic abnormality, and 5% of all MDS.

Deletions in the long arm of chromosome 20 are found in 5-10% of MDS patients. Although it’s not yet clear exactly which genes are responsible for the pathogenic effects of the deletion, several tumor suppressors have recently been identified as possible targets.

Monosomy 7 and del(7q) occur in 10% of de novo MDS and in 50% of therapy-related MDS. CUX1 and TES are 2 tumor suppressor genes found in 7q- commonly deleted regions; their loss is thought to promote MDS development.

While ETV6 rearrangements are recurrent in many myeloid and lymphoid malignancies, including MDS. The gene has been found fused to over 30 different partner genes, the identify of which can have important clinical implications.

The 11q23 region containing MLL is amplified in a significant portion of MDS and AML patients with complex karyotypes. Studies point to MLL amplification as causing genomic instability via overactivation of target genes like HOXA9 and MEIS1.

MECOM/RPN1 fusion subjects MECOM to RPN1’s promoter, leading to MECOM overexpression in myeloid cells. The fusion is considered primary driver in both MDS and AML, occurring in 2-3% of the latter.