Distribution of cytogenetic abnormalities in myelodysplastic syndromes, Philadelphia negative myeloproliferative neoplasms, and the overlap MDS/MPN category

Abstract

(2008), chronic myeloid malignancies are divided in myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), and overlap MDS/MPN cases. From morphological aspects, these categories show overlaps. To evaluate whether these morphological similarities have genetic parallels, we investigated 1,851 cases with suspected/confirmed myelodysplastic or myeloproliferative diseases by chromosome banding and molecular analyses. Cytogenetics revealed aberrant karyotypes in 354 patients (19.1% of the original cohort) who were the basis of further analysis. The distribution of chromosomal aberrations differed significantly between categories. Isolated +9 and gain of 9p were exclusively observed in MPN (+9: 10/93; 11%; p<0.001; +9p: 6/93; 7% of all aberrant MPN cases) but were not detected in MDS or MDS/MPN (p=0.001). Isolated del(5q) (p=0.002), −7 in combination with other aberrations (p=0.016), and complex aberrations (p=0.003) were 2.9-to 7.5-fold more frequent in MDS than in MPN. Trisomies 8 and 21 and del(20q) were comparably frequent in both subgroups. Interestingly, the MDS/MPN overlap cohort showed a higher frequency of −7 accompanied by other aberrations (3/17; 18% of all aberrant cases; p=0.001), i(17)(q10) (2/17; 12%; p=0.013), and +21 (2/17; 12%; p=0.013) when compared to MPN or MDS only. These differences support the category for MDS/MPN within the new WHO classification. Overlaps between the diverse disorders were seen also for the JAK2V617F (MPN 66/89; 74%; MDS/MPN 4/14; 29%; MDS 2/63; 3%) and NRAS mutations (MDS 2/67; 3%; MPN 2/4; MDS/MPN 1/1). In conclusion, cytogenetics and molecular genetics show overlaps in varying proportions of MDS and MPN cases which might indicate common pathways in their etiology. Some markers are strongly associated with one of these disorders and can be helpful for differential diagnosis especially in difficult cases.

Clinical significance of newly emerged isolated del(20q) in patients following cytotoxic therapies

“…Interestingly, other karyotypic alternations occurred in six of these nine patients at the time when therapy-related myeloid neoplasm was diagnosed: a minor clone evolved to a major clone in bone marrow (n = 3); clonal evolution (n = 2); or a new hypodiploid clone emerged (n = 1). These findings suggest that (1) detection of del(20q) clone can occur before the detection of cytopenia and/or dysplasia, which is consistent with the findings by Kanagal-Shamanna et al; 17 (2) clonal size is a very important risk factor for developing therapy-related myeloid neoplasm as mentioned above; (3) del(20q) may not be sufficient to cause therapy-related myeloid neoplasm in some patients and additional genetic changes are required to further potentiate the leukemic clone.…”

“…[1][2][3][4] The presence of del(20q) appears to be associated with a favorable prognosis and low risk for acute myeloid leukemia transformation in patients with Philadelphia chromosome-negative myeloproliferative neoplasms and myelodysplastic syndromes. [5][6][7][8] However, in patients with de novo acute myeloid leukemia, del(20q) has been associated with a poor response to chemotherapy and reduced overall survival, and has been classified as intermediate II risk category.…”

Clinical utility gene card for: familial polycythaemia vera

“…16 Prenatal testing is not indicated in familial PV (JAK2 V617F is a somatic mutation that occurs with disease manifestation after birth, and detection of non-V617F JAK2 germ-line polymorphisms or germ-line EGLN1 mutations have no consequence during pregnancy). Prenatal JAK2 V617F PV is extremely rare and is not associated with familial MPN.…”

Novel chromosomal translocation (17;22)(q12;q12) in a case of myelodisplastic syndrome characterized with signs of hemolytic anemia at presentation

“…Several genetic alterations such as translocations, gene mutations and deletions play a role in this process. However, approximately 50% of myelodysplastic syndromes (MDS) present a normal karyotype, while the remaining part has (simple or complex) cytogenetic aberrations at time of diagnosis (Bacher et al, 2009;Bernasconi et al, 2010;Haase, 2008;Valent and Wieser, 2009). Common recurrent cytogenetic abnormalities detected at diagnosis include, in order of decreasing frequency, −7/7q−, −5/5q−, + 8, 20q−, −Y, i(17q) or t(17p), −13/13q−, 11q−, 12p− or t(12p), with the most common abnormalities (−7/7q−, −5/5q−, +8 and 20q−) (Nolte and Hofmann, 2008).…”