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Myeloproliferative Neoplasms with Monocytosis

  • Myelodysplastic Syndromes and MPN/MDS Overlap (BL Stein, Section Editor)
  • Published:
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Abstract

Purpose of Review

Myeloproliferative neoplasms (MPN) are a heterogeneous group of hematopoietic stem cell neoplasms comprising of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) that share driver mutations (JAK2/CALR/MPL) resulting in constitutive activation of JAK/STAT and other signaling pathways. Patients with MPN have shortened survival and an inherent risk for leukemic evolution. Prognostically relevant clinical and genetic parameters have been incorporated into mutation-enhanced scoring systems (MIPSS70-plus version 2.0, MIPSS-ET/PV). In the current review, we describe clinical and pathological features along with prognostic significance of MPN with monocytosis.

Recent Findings

Monocytosis, defined by an absolute monocyte count (AMC) ≥ 1 × 10 9/L, is a typical manifestation of chronic myelomonocytic leukemia (CMML) but is also associated with 21% and 17% of PV and PMF patients, respectively. Recent studies on the subject have reported that MPN patients with monocytosis are older and present with concomitant leukocytosis. In regard to PV, patients with monocytosis harbor unfavorable cytogenetic abnormalities including +8, 7/7q, i(17q), 5/5q−,12p−, inv(3), or 11q23 rearrangement and SRSF2 mutations, whereas PMF patients with monocytosis had significant thrombocytopenia, higher circulating blasts, higher symptom burden, and ASXL1 mutations. Moreover, presence of monocytosis predicted inferior survival in both PV and PMF.

Summary

Monocytosis in MPN is associated with a distinct clinical and genetic profile and may serve as a marker of aggressive disease biology.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Patnaik MM, Tefferi A. CMML: 2018 update on diagnosis, risk stratification, and management. Am J Hematol. 2018;93(6):824–40.

    Article  CAS  Google Scholar 

  2. Eo WK, Kwon BS, Kim KH, Kim HY, Kim HB, Koh SB, et al. Monocytosis as a prognostic factor for survival in stage IB and IIA cervical cancer. J Cancer. 2018;9(1):64–70.

    Article  Google Scholar 

  3. Chen MH, Chang PMH, Chen PM, Tzeng CH, Chu PY, Chang SY, et al. Prognostic significance of a pretreatment hematologic profile in patients with head and neck cancer. J Cancer Res Clin Oncol. 2009;135(12):1783–90.

    Article  Google Scholar 

  4. Bari A, Tadmor T, Sacchi S, Marcheselli L, Liardo EV, Pozzi S, et al. Monocytosis has adverse prognostic significance and impacts survival in patients with T-cell lymphomas. Leuk Res [Internet] 2013;37(6):619–623. Available from: https://doi.org/10.1016/j.leukres.2013.01.009

  5. Takasaki Y, Iwanaga M, Tsukasaki K, Kusano M, Sugahara K, Yamada Y, et al. Impact of visceral involvements and blood cell count abnormalities on survival in adult T-cell leukemia/lymphoma (ATLL). Leuk Res. 2007;31(6):751–7.

    Article  Google Scholar 

  6. Barbui T, Thiele J, Gisslinger H, Kvasnicka HM, Vannucchi AM, Guglielmelli P, et al. The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion. Blood Cancer J [Internet]. 2018;8(2):15. Available from: https://doi.org/10.1038/s41408-018-0054-y

  7. Gangat N, Tefferi A. Myelofibrosis biology and contemporary management. Br J Haematol. 2020;

  8. Tefferi A, Guglielmelli P, Lasho TL, Gangat N, Ketterling RP, Pardanani A, et al. MIPSS701 version 2.0: mutation and karyotype-enhanced international prognostic scoring system for primary myelofibrosis. J Clin Oncol. 2018;36(17):1769–70.

    Article  Google Scholar 

  9. Barbui T, Vannucchi AM, Buxhofer-Ausch V, De Stefano V, Betti S, Rambaldi A, et al. Practice-relevant revision of IPSET-thrombosis based on 1019 patients with WHO-defined essential thrombocythemia. Blood Cancer J. 2015;5(11):2–4.

    Article  Google Scholar 

  10. Boiocchi L, Espinal-Witter R, Geyer JT, Steinhilber J, Bonzheim I, Knowles DM, et al. Development of monocytosis in patients with primary myelofibrosis indicates an accelerated phase of the disease. Mod Pathol. 2013;26(2):204–12.

    Article  CAS  Google Scholar 

  11. O’Sullivan J, Mead AJ. Heterogeneity in myeloproliferative neoplasms: causes and consequences. Adv Biol Regul. 2019;71(November 2018):55–68.

    Article  Google Scholar 

  12. Coltro G, Patnaik MM. Chronic myelomonocytic leukemia: insights into biology, prognostic factors, and treatment. Curr Oncol Rep. 2019;21(11).

  13. Swerdlow SH, Campo E, Lee Harris N, Jaffe ES, Pileri SA, Stein H, et al. WHO classification of tumours of haematopoietic and lymphoid tissues, 4th edition. Histopathology. 2017.

  14. Tefferi A. Primary myelofibrosis: 2019 update on diagnosis, risk-stratification and management. Am J Hematol. 2018;93(12):1551–60.

    Article  Google Scholar 

  15. Tefferi A, Barbui T. Polycythemia vera and essential thrombocythemia: 2017 update on diagnosis, risk-stratification, and management. Am J Hematol. 2017;92(1):94–108.

    Article  CAS  Google Scholar 

  16. Geyer H, Scherber R, Kosiorek H, Dueck AC, Kiladjian JJ, Xiao Z, et al. Symptomatic profiles of patients with polycythemia vera: implications of inadequately controlled disease. J Clin Oncol. 2016;34(2):151–9.

    Article  CAS  Google Scholar 

  17. •• Patnaik MM, Timm MM, Vallapureddy R, Lasho TL, Ketterling RP, Gangat N, et al. Flow cytometry based monocyte subset analysis accurately distinguishes chronic myelomonocytic leukemia from myeloproliferative neoplasms with associated monocytosis. Blood Cancer J. 2017;7(7):e584 This study reported the use of flow cytometry for determinate chronic myelomonocytic leukemia patients from myeloproliferative neoplasm patients with associated monocytosis. Patnaik et al. also compared clinical and laboratory features between these diseases.

    Article  CAS  Google Scholar 

  18. Tefferi A, Guglielmelli P, Larson DR, Finke C, Wassie EA, Pieri L, et al. Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood. 2014;124(16):2507–13.

    Article  CAS  Google Scholar 

  19. Petrova-Drus K, Chiu A, Margolskee E, Barouk-Fox S, Geyer J, Dogan A, et al. Bone marrow fibrosis in chronic myelomonocytic leukemia is associated with increased megakaryopoiesis, splenomegaly and with a shorter median time to disease progression. Oncotarget. 2017;8(61):103274–82.

    Article  Google Scholar 

  20. Wong KL, Tai JJY, Wong WC, Han H, Sem X, Yeap WH, et al. Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets. Blood. 2011;118(5):16–31.

    Article  Google Scholar 

  21. Selimoglu-Buet D, Wagner-Ballon O, Saada V, Bardet V, Itzykson R, Bencheikh L, et al. Characteristic repartition of monocyte subsets as a diagnostic signature of chronic myelomonocytic leukemia. Blood. 2015;125(23):3618–27.

    Article  CAS  Google Scholar 

  22. Elena C, Gallì A, Such E, Meggendorfer M, Germing U, Rizzo E, et al. Integrating clinical features and genetic lesions in the risk assessment of patients with chronic myelomonocytic leukemia. Blood. 2016;128(10):1408–17.

    Article  CAS  Google Scholar 

  23. Chapman J, Geyer JT, Khanlari M, Moul A, Casas C, Connor ST, et al. Myeloid neoplasms with features intermediate between primary myelofibrosis and chronic myelomonocytic leukemia. Mod Pathol [Internet]. 2018;31(3):429–441. Available from: https://doi.org/10.1038/modpathol.2017.148

  24. Beran M, Shen Y, Onida F, Wen S, Kantarjian H, Estey E. Prognostic significance of monocytosis in patients with myeloproliferative disorders. Leuk Lymphoma. 2006;47(3):417–23.

    Article  Google Scholar 

  25. Verma D, Kantarjian HM, Jones D, Luthra R, Borthakur G, Verstovsek S, et al. Chronic myeloid leukemia with P190 BCR-ABL. Blood. 2009;114(11):2232–5.

    Article  CAS  Google Scholar 

  26. • Cargo C, Cullen M, Taylor J, Short M, Glover P, Van Hoppe S, et al. The use of targeted sequencing and flow cytometry to identify patients with a clinically significant monocytosis. Blood. 2019;133(12):1325–34 This study evaluated 283 patients with monocytosis finding that somatic mutations were detected at high frequency independently from the diagnosis and suggested the present of a “clonal monocytosis of clinical significance” with prognostic relevance.

    Article  CAS  Google Scholar 

  27. Cazzola M. Clonal monocytosis of clinical significance. Blood. 2019;133(12):1271–2.

    Article  CAS  Google Scholar 

  28. Tefferi A, Barbui T. Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk-stratification and management. Am J Hematol. 2019;94(1):133–43.

    Article  Google Scholar 

  29. Tefferi A, Rumi E, Finazzi G, Gisslinger H, Vannucchi AM, Rodeghiero F, et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia. 2013;27(9):1874–81.

    Article  CAS  Google Scholar 

  30. Tefferi A, Guglielmelli P, Lasho TL, Coltro G, Finke CM, Loscocco GG, et al. Mutation-enhanced international prognostic systems for essential thrombocythaemia and polycythaemia vera. Br J Haematol. 2020;189(2):291–302.

    Article  CAS  Google Scholar 

  31. •• Barraco D, Cerquozzi S, Gangat N, Patnaik MM, Lasho T, Finke C, et al. Monocytosis in polycythemia vera: clinical and molecular correlates. Am J Hematol. 2017;92(7):640–5 This study investigated the clinical and laboratory features of polycythemia vera patients with associated monocytosis. Barraco et al. proved the negative prognostic impact of monocytosis.

    Article  CAS  Google Scholar 

  32. Tefferi A, Guglielmelli P, Lasho TL, Gangat N, Ketterling RP, Pardanani A, et al. MIPSS701 version 2.0: mutation and karyotype-enhanced international prognostic scoring system for primary myelofibrosis. J Clin Oncol. 2018;36(17):1769–70.

    Article  Google Scholar 

  33. Nicolosi M, Mudireddy M, Lasho TL, Hanson CA, Ketterling RP, Gangat N, et al. Sex and degree of severity influence the prognostic impact of anemia in primary myelofibrosis: analysis based on 1109 consecutive patients. Leukemia. 2018;32(5):1254–8.

    Article  Google Scholar 

  34. Tefferi A, Nicolosi M, Mudireddy M, Lasho TL, Gangat N, Begna KH, et al. Revised cytogenetic risk stratification in primary myelofibrosis: analysis based on 1002 informative patients. Leukemia. 2018;32(5):1189–99.

    Article  Google Scholar 

  35. •• Tefferi A, Shah S, Mudireddy M, Lasho TL, Barraco D, Hanson CA, et al. Monocytosis is a powerful and independent predictor of inferior survival in primary myelofibrosis. Br J Haematol. 2018;183(5):835–8 In this study, Tefferi et al. identified clinical characteristics of primary myelofibrosis with monocytosis and confirmed the presence of monocytosis as a predictor of inferior survival.

    Article  Google Scholar 

  36. • Elliott MA, Verstovsek S, Dingli D, Schwager SM, Mesa RA, Li CY, et al. Monocytosis is an adverse prognostic factor for survival in younger patients with primary myelofibrosis. Leuk Res. 2007;31(11):1503–9 In this study, for the first time, monocytosis was found an adverse prognostic factor for survival.

    Article  CAS  Google Scholar 

  37. Huang J, Li CY, Mesa RA, Wu W, Hanson CA, Pardanani A, et al. Risk factors for leukemic transformation in patients with primary myelofibrosis. Cancer. 2008;112(12):2726–32.

    Article  Google Scholar 

  38. McNamara CJ, Panzarella T, Kennedy JA, Arruda A, Claudio JO, Daher-Reyes G, et al. The mutational landscape of accelerated- and blast-phase myeloproliferative neoplasms impacts patient outcomes. Blood Adv. 2018;2(20):2658–71.

    Article  CAS  Google Scholar 

  39. Tam CS, Kantarjian H, Cortes J, Lynn A, Pierce S, Zhou L, et al. Dynamic model for predicting death within 12 months in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis. J Clin Oncol. 2009;27(33):5587–93.

    Article  Google Scholar 

  40. Gangat N, Morsia E, Foran JM, Palmer JM, Elliott MA, Tefferi A. Venetoclax plus hypomethylating agent in blast-phase myelo-proliferative neoplasm: preliminary experience with 12 patients. Br J Haematol. 2020.

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Authors and Affiliations

  1. Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA

    Erika Morsia & Naseema Gangat

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  1. Erika Morsia
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Correspondence to Naseema Gangat.

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This article is part of the Topical Collection on Myelodysplastic Syndromes and MPN/MDS Overlap

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Morsia, E., Gangat, N. Myeloproliferative Neoplasms with Monocytosis. Curr Hematol Malig Rep 17, 46–51 (2022). https://doi.org/10.1007/s11899-021-00660-2

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