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Chronic myeloproliferative neoplasms

Cytogenetic clonal evolution in myeloproliferative neoplasms: contexts and prognostic impact among 648 patients with serial bone marrow biopsies

Leukemia volume 33, pages 2522–2553 (2019)Cite this article

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Karyotype is diagnostically and prognostically essential in patients with myeloproliferative neoplasms (MPN); cytogenetic abnormalities occur in approximately a third of patients with primary myelofibrosis (PMF) [1] and 5–20% of those with essential thrombocythemia (ET) [2] or polycythemia vera (PV) [3]. “Abnormal” karyotype in PV [3] and “unfavorable” or “very high risk (VHR)” karyotype in PMF [1] have been associated with inferior survival. In PV, median survivals were estimated at 9 years for patients with abnormal karyotype vs. 14 years for those with normal karyotype [3]. In PMF, median survival estimates were 4.4 years for “favorable” karyotype (i.e. normal karyotype or sole abnormalities of 13q−, + 9, 20q−, chromosome 1 translocation/duplication or sex chromosome abnormality including –Y), 1.2 years for VHR karyotype (i.e. single or multiple abnormalities of −7, i(17q), inv(3)/3q21, 12p−/12p11.2, 11q−/11q23, or other autosomal trisomies not including +8/+9) and 2.9 years for “unfavorable” karyotype (i.e. all other abnormalities) [1]. It is currently not known if acquisition of cytogenetic abnormalities during the clinical course of MPN carries similar prognostic relevance. The main objective of the current retrospective study was to examine the incidence and pattern of changes in karyotype of patients with MPN and their impact on survival.

After approval from the Mayo Clinic institutional review board, study patients were recruited from institutional databases, based on documentation of at least two serial bone marrow (BM) biopsies. Diagnoses were according to the 2016 World Health Organization criteria [4]. Cytogenetic analysis and reporting was done according to the International System for Human Cytogenetic Nomenclature (ISCN) criteria [5]. Cytogenetic analysis in all instances was performed on fresh BM aspirates, placed in hypotonic trypsin–colcemid solution and processed according to standard techniques for chromosome analysis using Giemsa/ Trypsin/Leishman (GTL) banding with trypsin and Leishman stain [6]. Thrombolytic agents were added to clotted BM specimens in order to improve success rates [7]. Chromosomal abnormalities were considered clonal if the same structural abnormality or extra chromosome appears in at least 2 and monosomy in at least 3 metaphases; [5] a normal karyotype required at least 10 metaphases evaluated and absence of any clonal abnormalities, including loss of Y. In addition to documenting the presence or absence of changes in karyotype, a notation was made regarding disease phase, at the time of the repeat biopsy, in order to allow accurate interpretation of the data and evaluation of survival impact. Statistical analyses considered clinical and laboratory data collected at the time of collection of BM for cytogenetic studies. Survival was calculated from the time point of documented change in karyotype. JMP® Pro 13.0.0 software from SAS Institute, Cary, NC, USA, was used for all statistical calculations.

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Authors and Affiliations

  1. Divisions of Hematology, Departments of Internal Medicine and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA

    Ayalew Tefferi, Maura Nicolosi, Domenico Penna, Rangit Vallapureddy, Animesh Pardanani & Naseema Gangat

  2. Divisions of Hematopathology, Departments of Internal Medicine and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA

    Curtis A. Hanson

  3. Divisions of Laboratory Genetics and Genomics, Departments of Internal Medicine and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA

    Rhett P. Ketterling

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  1. Ayalew Tefferi
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  2. Maura Nicolosi
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  3. Domenico Penna
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  4. Rangit Vallapureddy
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  5. Curtis A. Hanson
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  7. Naseema Gangat
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  8. Rhett P. Ketterling
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Contributions

All authors have reviewed the manuscript and gave their approval. AT designed the study, contributed patients, helped with abstract patient information, performed statistical analysis and wrote the paper; MN was primarily involved in data abstraction and preparation of tables; AP and NG contributed patients and helped with abstract patient information; RPK was in charge of cytogenetic information; CAH was in charge of information on pathology; DP and RV helped with original abstraction of clinical and laboratory information from patient histories.

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Correspondence to Ayalew Tefferi.

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Tefferi, A., Nicolosi, M., Penna, D. et al. Cytogenetic clonal evolution in myeloproliferative neoplasms: contexts and prognostic impact among 648 patients with serial bone marrow biopsies. Leukemia 33, 2522–2553 (2019). https://doi.org/10.1038/s41375-019-0453-5

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