Abstract 3549

Acute myeloid leukemia and myelodysplastic syndrome cases with monosomy 7 or del(7q) comprise a heterogeneous group. Complex karyotypes with multiple aberrations such as del(5q) are more frequent, and there is evidence that the overall survival is significantly lower in this group, compared with patients who have monosomy 7 or del(7q) as a sole abnormality. In this study, our purpose was to gain insights into these heterogeneous subsets among myeloid disorders with lesions of chromosome 7, taking advantage of the better definition of chromosomal aberrations which provides SNP-A karyotyping.

We studied a large cohort of patients (N=1,153) with myeloid disorders using SNP-A karyotyping. Loss of heterozygosity (LOH) in 7q was identified in 9.7% (112/1153) of patients. It included monosomy 7 (n=38, 3.3%), del(7q) (n=55, 4.8%) and UPD7 (n=19, 1.6%). The LOH 7 cohort included men (70%) and women (30%) with a mean age of 57 years (S.D. 22.2 years). The presence of chromosome 7 material in 35% of our cases with apparent monosomy 7 by conventional MC serves as an illustration for SNP array-based mapping allowing for a more precise definition of the breakpoints. Clinical and chromosomal lesions association made possible to distinguish between three subsets: UPD 7: with 60% of the patients included in a myeloproliferative or myeloproliferative/myelodysplastic disease and 50% of presence of EZH2 mutations; del(7q): with 85% of patients included in the high risk group (RAEB and AML) and frequently associated with complex karyotypes (including 5q and 17p LOH); and monosomy 7: frequently (59%) as a sole abnormality and, in the case of MDS patients, associated with hypoplastic features. The existence of those three subsets is supported by the difference survival among the MDS cohort: median overall survival of 1250, 512 and 209 days for UPD 7, monosomy 7 and del(7q) patients, respectively (p=0.03). Three SNP-A defined commonly deleted regions were described in bands 7q22 (100634238–101658775), 7q34 (137841484–139319208), and between bands 7q35 and 7q35q36.1 (144338001–148545983) but among the candidate tumor suppressor genes (TSG), only EZH2 showed to be recurrently mutated in UPD7. The lack of a TSG mutation in monosomy and del(7q) cases led us to determine that the expression of majority of genes included in the CDRs was significantly reduced in MDS CD34+ cells from 9 cases with monosomy or partial deletion of chromosome 7 (Multiple testing by Benjamin Hochberg correction, FDR<10%). These genes included LUC7L2, ZNHIT1, TTC26, RABL5, TRIM24, EZH2, ZC3HAV1L, CNTNAP2, TRIM24, CUX1, FIS1, RABL5, ZC3HAV1 and TBXAS. The mean decrease in gene expression was 42–33 % supporting haploinsufficiency as a probable cause of disease.

In summary, the present study shows how SNP-A karyotyping enables us to refine our knowledge about lesions of chromosome 7. The secondary nature of del(7q), accompanied almost invariably by “founder” 5q aberrations, the proliferative phenotype and presence of EZH2 mutations of UPD7q, and the description of monosomy 7 as isolated lesion and associated with hypoplastic disease phenotype, are the main correlations found herein, which prompt to investigate for different underlying pathogenic origin for each subset.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.