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Essential thrombocythaemia with mutation in MPL: clinicopathological correlation and comparison with JAK2V617F-mutated and CALR-mutated genotypes
  1. Alberto Alvarez-Larran1,
  2. Daniel Martínez2,
  3. Leonor Arenillas3,
  4. Ariadna Rubio4,
  5. Eduardo Arellano-Rodrigo5,
  6. Juan Carlos Hernández Boluda6,
  7. Natalia Papaleo3,
  8. Gonzalo Caballero7,
  9. Clara Martínez8,
  10. Francisca Ferrer-Marín9,
  11. María Isabel Mata10,
  12. Manuel Pérez-Encinas11,
  13. María Antonia Durán12,
  14. José María Alonso13,
  15. Gonzalo Carreño-Tarragona14,
  16. Juan Manuel Alonso15,
  17. Soledad Noya16,
  18. Elena Magro17,
  19. Raúl Pérez18,
  20. Mónica López-Guerra2,
  21. Irene Pastor-Galán6,
  22. Francisco Cervantes1,
  23. Carlos Besses4,
  24. Luis Colomo3,
  25. María Rozman2
  1. 1 Hematology Department, Hospital Clínic-IDIBAPS, Barcelona, Spain
  2. 2 Pathology Department, Hospital Clínic-IDIBAPS, Barcelona, Spain
  3. 3 Pathology Department-IMIM, Hospital del Mar, Universidad Autónoma de Barcelona, Barcelona, Spain
  4. 4 Hematology Department-IMIM, Hospital del Mar, Universitat Autónoma de Barcelona, Barcelona, Spain
  5. 5 Hemotherapy and Hemostasis Department, Hospital Clínic-IDIBAPS, Barcelona, Spain
  6. 6 Hematology Department, Hospital Clínico-INCLIVA, Valencia, Spain
  7. 7 Hematology Department, Hospital Miguel Servet, Zaragoza, Spain
  8. 8 Hematology Department, Hospital Sant Pau, Barcelona, Spain
  9. 9 Hematology and Medical Oncology, Hospital Morales-Messeguer, CIBERER, UCAM, Murcia, Spain
  10. 10 Hematology Department, Hospital de la Costa del Sol, Marbella, Spain
  11. 11 Hematology Department, Hospital Clínico, Santiago de Compostela, Spain
  12. 12 Hematology Department, Hospital Son Espases, Palma de Mallorca, Spain
  13. 13 Hematology Department, Hospital de Palencia, Palencia, Spain
  14. 14 Hematology Department, Hospital 12 de Octubre, Madrid, Spain
  15. 15 Hematology Department, Fundación Jiménez Díaz, Madrid, Spain
  16. 16 Hematology Department, Complexo Hospitalario, A Coruña, Spain
  17. 17 Hematology Department, Hospital Príncipe de Asturias, Alcalá de Henares, Spain
  18. 18 Hematology Department, Hospital Virgen de la Arrixaca, Murcia, Spain
  1. Correspondence to Dr Alberto Alvarez-Larran, Hematology Department, Hospital Clínic, Barcelona 08034, Spain; aalvar{at}clinic.ub.es

Abstract

Aim To characterise the clinical and histological features of MPL-mutated essential thrombocythaemia (ET).

Patients and methods Bone marrow biopsies of 175 patients with ET were centrally reviewed according to the 2016 WHO classification, including 42 cases with MPL mutation, 98 JAK2V617F-mutated and 35 CALR-mutated. Clinical and histological features were compared among the three genotypes included in the current 2016 WHO classification and among the different types of MPL mutations.

Results Patients with MPL-mutated ET were significantly older than those with the other genotypes. Haematological values at diagnosis were similar among MPL-mutated and CALR-mutated ET, with both genotypes showing higher platelet counts and lower haemoglobin values than ET with JAK2V617F genotype. In the bone marrow, the median number of megakaryocytes was higher in MPL and CALR than in JAK2V617F genotype (16, 19 and 14 megakaryocytes per ×20 power field, respectively, p=0.004). Histological features of prefibrotic myelofibrosis were rarely observed in MPL genotype, whereas sinusoidal hyperplasia, dense clusters of megakaryocytes and reticulin fibrosis were more frequent in CALR-mutated ET, with 11% of such cases fulfilling WHO 2016 histological criteria of prefibrotic myelofibrosis. With a median follow-up of 3.5 years, no significant differences were seen among genotypes regarding survival, vascular complications or myelofibrotic transformation. There were no significant differences in the clinical data or in the histological characteristics depending on the type of MPL mutation.

Conclusion MPL and CALR ET genotypes share clinical and histological characteristics. In contrast to CALR genotype, features of prefibrotic myelofibrosis are uncommon in MPL-mutated ET.

  • essential thrombocythemia
  • diagnostic hematology
  • histopathology
  • genetics
  • myeloproliferative neoplasms

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Footnotes

  • Handling editor Mary Frances McMullin.

  • Contributors AA-L designed the study, collected the data, performed the statistical analysis, analysed and interpreted the results, and wrote the paper. DM, LA, LC and MR reviewed the bone marrow biopsies, interpreted the results and wrote the paper. AR collected the data, performed statistical analysis and approved the final version. NP reviewed the bone marrow biopsies and approved the final version. EA-R, JoMA, SN, GC-T, FF-M, MAD, MP-E, JuMA, MIM, EM, CM and IP-G collected the data and approved the final version. ML-G performed the molecular studies and approved the final version. JCHB, FC and CB collected the data, interpreted the results and wrote the paper.

  • Funding This work was supported by grants from the Instituto de Salud Carlos III (PI13/00557, PI13/0636, PI1300393 and RD12/0036/0010).

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval Hospital del MAR IRB.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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