The Type of Genetic Abnormalities Causing Loss of 5q Varies Between MDS and AML and Is Associated with Worse Prognosis in MDS

Deletions of the long arm of chromosome 5 are frequent abnormalities in MDS and AML. Their size varies considerably. Two commonly deleted regions (CDR) have been described on 5q: a distal CDR deleted in the 5q- syndrome and a proximal region lost in higher-risk MDS and AML. However, the majority of MDS and AML patients with del(5q) show large deletions encompassing both CDRs. Recently, Jerez et al. (JCO 2012) reported on commonly retained regions (CRRs) using SNP arrays and observed that deletions involving the centromeric and telomeric extremes of 5q are associated with a more aggressive clinical course. From a cytogenetic view loss of 5q either occurs due to interstitial deletions, unbalanced translocations or monosomy 5. While in interstitial deletions the telomeric region of 5q is retained, this region is lost in cases with unbalanced 5q translocations and monosomy 5.

Analyze whether the type of 5q loss (interstitial deletion vs unbalanced translocation/ monosomy) is associated with other biological markers and prognosis in AML and MDS.

In total, 1,200 patients (pts) with loss of 5q were studied including 627 AML pts (de novo: 454, s-AML: 101, t-AML: 72) and 573 MDS pts (de novo: 511, t-MDS: 62) with a median age of 71.7 yrs (range: 30–90) and 73.2 yrs (range: 34–93). Interphase FISH had been performed in all pts with a probe for EGR1 (5q31) and all showed a heterozygous EGR1 deletion. Further, all cases had been studied by chromosome banding analysis and in addition by 24-color FISH whenever necessary to resolve complex karyotypes. Data on TP53 mutation status was available in 263 pts (AML: 152, MDS: 111).

1. Loss of 5q due to unbalanced translocations encompassing the telomeric 5q region is more frequent in AML (45.6%) than in MDS (32.8%) and in both entities associated with a complex karyotype. MDS patients with unbalanced 5q translocations show a shorter survival as compared to patients with interstitial 5q deletions. This data suggests that in MDS unbalanced 5q translocations reflect chromosomal instability which most probably is associated with progression to AML and adverse prognosis. 2. In AML with loss of 5q the presence of TP53 mutations is the strongest adverse prognostic factor.

Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership. Grossmann:MLL Munich Leukemia Laboratory: Employment. Kohlmann:MLL Munich Leukemia Laboratory: Employment. Schnittger:MLL Munich Leukemia Laboratory: Equity Ownership. Kern:MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership.