A literature review focused on the prognostic role of cytogenetics in Philadelphia (Ph)-negative myeloproliferative neoplasms (MPN) was recently published in Medicina.

In the article, the authors concentrated on the most prevalent Ph-negative MPN classifications: polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis.

Cytogenetics has a well-established prognostic role in acute leukemias and in myelodysplastic syndromes, where it drives clinical decisions, and the cytogenetics analysis in Ph-negative MPNs can similarly offer useful information on prognosis.

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Although the natural histories of Ph-negative MPNs can sometimes last decades, the authors point out that over that time, altered DNA methylation, which is associated with age and mutations, can also cause DNA breakage that can lead to deletions and duplications. Along with acquired point mutations and telomere shortening, these chromosomal alterations are also prognostically important for leukemic transformation.

The conventional method for cytogenetics is G-banding of metaphase nuclei from a cell culture to obtain a karyotype. Additional techniques include fluorescence in situ hybridization with labeled DNA probes, and hybridization with protein nucleic acid probes.

Common cytogenetics alterations that are not specific to a single disease but are found across myeloid malignancies include Del(20q), Del(13q), chromosome 1 abnormalities, +8, +9, Del(13q), Del(11q), +21, +15, Del(5q), i(17q), -7, and Del(7q).

In the setting of primary myelofibrosis, the prognostic role of cytogenetics is currently used to guide treatment options in scores (including DIPSS-plus and MIPSS70-plus 2.0); whereas, in other MPNs, it is was found to be not as well defined and not used routinely to inform treatment decisions, including in secondary myelofibrosis.

Studies in PV have suggested the importance of obtaining cytogenetic information, as an abnormal karyotype at time of diagnosis appears to have a prognostic impact on overall survival and leukemia-free survival; however, the authors indicate that further confirmation studies are needed.

In ET, few studies, often with few patients, have been published to date on the prognostic impact of cytogenetics, making difficult to describe its relevance; additional studies are needed.

“[W]e suggest that cytogenetics (considering its availability and relative cost) should be performed in every suspected myelofibrosis and could be performed in myeloproliferative neoplasms at diagnosis or at the time of suspected transformation,” the authors wrote. “Determining a baseline karyotype helps the clinician determine prognosis in MF, PV, and [systemic mastocytosis]; the prognostic value in ET, [unclassifiable MPN], [chronic neutrophilic leukemia], and [chronic eosinophilic leukemia] is unclear, but in these diseases, the cytogenetics analysis at diagnosis can give information about clonal evolution and track clonal changes at the time of transformation.”

Limitations and drawbacks of cytogenetics in the setting of Ph-negative MPNs include the need to perform the analysis on a fresh and adequate sample; the cell culture may not yield enough metaphase nuclei for the analysis; and an experienced operator should perform the G-banded karyotype.


Lanzarone G, Olivi M. The prognostic role of cytogenetics analysis in Philadelphia negative myeloproliferative neoplasms. Medicina (Kaunas). 2021;57(8):813. doi:10.3390/medicina57080813