Myelodysplastic Syndromes and Philadelphia Negative Chronic Myeloproliferative Diseases Show an Overlapping Pattern of Cytogenetic Aberrations.
Authors: Haferlach Claudia , Schnittger Susanne , Kern Wolfgang , Haferlach Torsten 
Published: April 2020

Abstract
The WHO classification introduced 3 categories:
chronic myeloproliferative diseases (CMPD) myelodysplastic/myeloproliferative diseases (MDS/CMPD) and myelodysplastic syndromes (MDS).
The aim was to analyze the pattern of cytogenetic aberrations in these categories excluding CML. In total 1996 cases belonging to these subgroups were referred to our laboratory and analyzed by chromosome banding analysis and cytomorphology. By cytomorphology 438 cases were classified as CMPD, 608 as MDS and 147 as MDS/CMPD. In 350 patients cytomorphology suspected a CMPD (CMPD-s) and in 423 a suspected MDS (MDS-s) but not all requested cytomorphologic criteria were fulfilled in these cases. Chromosome aberrations were detected in 81 of 438 CMPD (18.5%), 232 of 608 MDS (38.2%), 38 of 147 MDS/CMPD (25.9%), 33 of 350 CMPD-s (9.4%) and 71 of 423 MDS-s (16.8%). Therefore, 455 cases showing chromosome aberrations were identified and are the basis for aberration pattern analysis. In all three cytomorphologic categories balanced rearrangements were rare (n=40). The only recurring ones were 3q26-rearrangements (n=4). The most frequent aberrations were +1q (n=22), +8 (n=82, as the sole abnormality n=46), +9p (n=28) and +21 (n=16), i(17)(q10) (n=11), −7 (n=39, as the sole abnormality n=16), and loss of 5q (n=117), 5q deletion as the sole abnormality (n=45), 11q- (n=11), 12p- (n=21), 13q- (n=5), 20q- (n=59, as the sole abnormality n=41), and loss of the Y-chromosome (n=69). A complex aberrant karyotype (≥3 aberrations) was observed in 71 cases. None of these abnormalities was specific for one category. However, the following aberrations were significantly more frequently observed in CMPD as compared to MDS: +1q (10.6% vs 2.6%, p=0.001), +9p (23.0% vs. 0.3%, p&lt;0.0001), +9 sole (8.8% vs. 0.0%. p&lt;0.0001), and balanced rearrangements (15.0% vs. 6.3%. p=0.005). On the other hand the following aberrations were significantly more frequently observed in MDS as compared to CMPD: -Y (18.2% vs. 7.9%. p=0.01), deletion 5q (34.4% vs. 8.8%. p&lt;0.0001), deletion 5q sole (13.9% vs. 2.7%. p=0.001), −7 (9.6% vs. 4.4%. p=0.04), complex aberrant karyotype (18.5% vs. 9.7%. p=0.03). A comparison of the frequencies of abnormalities between MDS/CMPD and CMPD and MDS, respectively, revealed that +8 as the sole abnormality and +21 were significantly more frequent in MDS/CMPD as compared to CMPD or MDS (+8 sole: 21.0% vs 6.2% vs 10.3%, p=0.008 and p=0.05, respectively; +21: 23.6% vs. 0.9% vs 3.3%, p=0.001 and p=0.005, respectively). Deletion 5q and 5q- as the sole abnormality was significantly more frequent in MDS as compared to CMPD/MDS (34.4% vs. 7.9%, p=0.001 and 13.9% vs 0%, p=0.014), while +9 as the sole abnormality was less frequently found in MDS compared to CMPD/MDS (0% vs 2.6%, p=0.005). Trisomy 9p was significantly more frequent in CMPD as compared to CMPD/MDS (23.6% vs. 2.6%, p=0.005), while monosomy 7 as the sole abnormality was less frequently found in CMPD as compared to CMPD/MDS (0.9% vs 7.9%, p=0.02). In conclusion, MDS and CMPD show an overlapping pattern of cytogenetic aberrations with aberrations such as +8, loss of 11q, 12p, 13q and 20q occurring with comparable frequencies. However, trisomy 1q and 9p were observed more frequently in CMPD while -Y, 5q deletion, monosomy 7 and complex aberrant karyotype were predominantly found in MDS. Also from the cytogenetic point of view CMPD/MDS cases are not distinguishable from either MDS or CMPD. However, +21 and +8 as the sole abnormality are more frequently observed in MDS/CMPD as compared to CMPD and MDS.