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Polyploidy in myelofibrosis: analysis by cytogenetic and SNP array indicates association with advancing disease
Nisha R Singh1, Christine M Morris, Mary Koleth
1Northern Blood Research Centre, Kolling Institute, University of Sydney, Sydney, Australia. nsingh@nsccahs.health.nsw.gov.au.
Background:
Myelofibrosis occurs as primary myelofibrosis or as a late occurrence in the evolution of essential thrombocythaemia and polycythaemia vera. It is the rarest of the three classic myeloproliferative neoplasms (MPN). Polyploidy has only rarely been reported in MPN despite the prominent involvement of abnormal megakaryocytes. The use of peripheral blood samples containing increased numbers of haematopoietic progenitors has improved the output from cytogenetic studies in myelofibrosis and together with the use of single nucleotide polymorphism arrays (SNPa) has contributed to an improved knowledge regarding the diverse genetic landscape of this rare disease.
Results:
Cytogenetic studies performed on a consecutive cohort of 42 patients with primary or post ET/PV myelofibrosis showed an abnormal karyotype in 24 cases and of these, nine showed a polyploid clone. Six of the nine cases showed a tetraploid (4n) subclone, whereas three showed mixed polyploid subclones with both tetraploid and octoploid (4n/8n) cell lines. The abnormal clone evolved from a near diploid karyotype at the initial investigation to a tetraploid karyotype in follow-up cytogenetic analysis in four cases. In total, six of the nine polyploid cases showed gain of 1q material. The remaining three cases showed polyploid metaphases, but with no detectable structural karyotypic rearrangements. Three of the nine cases showed chromosome abnormalities of 6p, either at diagnosis or later acquired. SNPa analysis on eight polyploid cases showed additional changes not previously recognised by karyotype analysis alone, including recurring changes involving 9p, 14q, 17q and 22q. Except for gain of 1q, SNPa findings from the polyploid group compared to eight non-polyploid cases with myelofibrosis found no significant differences in the type of abnormality detected.
Conclusions:
The study showed the use of peripheral blood samples to be suitable for standard karyotyping evaluation and DNA based studies. The overall profile of abnormalities found were comparable with that of post-MPN acute myeloid leukaemia or secondary myelodysplastic syndrome and cases in the polyploidy group were associated with features of high risk disease. The above represents the first documented series of polyploid karyotypes in myelofibrosis and shows a high representation of gain of 1q.
Insights
This study identifies polyploid karyotypes in myelofibrosis (MF), a rare myeloproliferative neoplasm (MPN). Polyploidy, particularly with gain of 1q, is linked to high-risk disease features in MF patients.
Area of Science:
- Hematology
- Genetics
- Oncology
Background:
- Myelofibrosis (MF) is a rare myeloproliferative neoplasm (MPN), often evolving from essential thrombocythaemia (ET) or polycythaemia vera (PV).
- Polyploidy is infrequently reported in MPN, despite abnormal megakaryocyte involvement.
- Advances in cytogenetic analysis using peripheral blood and single nucleotide polymorphism arrays (SNPa) enhance understanding of MF genetics.
Purpose of the Study:
- To investigate the occurrence and characteristics of polyploidy in myelofibrosis.
- To analyze genetic abnormalities associated with polyploidy in MF using karyotyping and SNPa.
- To determine the clinical significance of polyploidy in MF.
Main Methods:
- Karyotyping and single nucleotide polymorphism array (SNPa) analysis were performed on peripheral blood samples from 42 MF patients.
- Cytogenetic studies identified abnormal karyotypes in 24 patients, with nine exhibiting polyploid clones (tetraploid or mixed tetraploid/octoploid).
- SNPa analysis provided further genetic insights, identifying changes not detected by karyotyping alone.
Main Results:
- Nine out of 42 MF patients presented with polyploid clones, including tetraploid (4n) and mixed (4n/8n) cell lines.
- Four cases showed evolution from a near-diploid to a tetraploid karyotype over time.
- Gain of 1q material was observed in six polyploid cases; SNPa revealed additional recurring changes (9p, 14q, 17q, 22q).
Conclusions:
- Peripheral blood is suitable for cytogenetic and DNA-based studies in MF.
- Polyploid karyotypes in MF are associated with high-risk disease features, comparable to post-MPN acute myeloid leukemia or secondary myelodysplastic syndrome.
- This study is the first to document polyploid karyotypes in MF, highlighting a high incidence of gain of 1q.
