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Myeloproliferative neoplasm

December 01, 2023

Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers in which excess red blood cells, white blood cells or platelets are produced in the bone marrow. Myelo refers to the bone marrow, proliferative describes the rapid growth of blood cells and neoplasm describes that growth as abnormal and uncontrolled.

Myeloproliferative neoplasm
Other namesMyeloproliferative diseases (MPDs)
Myelogram of someone with a myeloproliferative disorder.
SpecialtyHematology and oncology

The overproduction of blood cells is often associated with a somatic mutation, for example in the JAK2, CALR, TET2, and MPL gene markers.

In rare cases, some MPNs such as primary myelofibrosis may accelerate and turn into acute myeloid leukemia.[1]

Classification edit

MPNs are classified as blood cancers by most institutions and organizations.[2] In MPNs, the neoplasm (abnormal growth) starts out as benign and can later become malignant.

As of 2016, the World Health Organization lists the following subcategories of MPNs:[3]

Causes edit

MPNs arise when precursor cells (blast cells) of the myeloid lineages in the bone marrow develop somatic mutations which cause them to grow abnormally. There is a similar category of disease for the lymphoid lineage, the lymphoproliferative disorders acute lymphoblastic leukemia, lymphomas, chronic lymphocytic leukemia and multiple myeloma.[4] Genetics is believed to play a central role in the development of MPNs, specially in developing thromboembolic and bleeding complications.[5]

Diagnosis edit

People with MPNs might not have symptoms when their disease is first detected via blood tests.[6] Depending on the nature of the myeloproliferative neoplasm, diagnostic tests may include red cell mass determination (for polycythemia), bone marrow aspirate and trephine biopsy, arterial oxygen saturation and carboxyhaemoglobin level, neutrophil alkaline phosphatase level, vitamin B12 (or B12 binding capacity), serum urate[7] or direct sequencing of the patient's DNA.[8] According to WHO diagnostic criteria published in 2016, myeloproliferative neoplasms are diagnosed as follows:[9]

Chronic myeloid leukemia edit

Chronic myeloid leukemia (CML) has a presence of the hallmark Philadelphia Chromosome (BCR-ABL1) mutation.

Chronic neutrophilic leukemia edit

Chronic neutrophilic leukemia (CNL) is characterized by a mutation in the CSF3R gene and an exclusion of other causes of neutrophilia.

Essential thrombocythemia edit

Essential thrombocythemia (ET) is diagnosed with a platelet count greater than 450 × 109/L and is associated with the JAK2 V617F mutation in up to 55% of cases[10] and with an MPL (thrombopoietin receptor) mutation in up to 5% of cases:.[11] There should be no increase in reticulin fibers and the patient should not meet the criteria for other MPNs, in particular Pre-PMF.

Polycythemia vera edit

Polycythemia vera (PV) is associated most often with the JAK2 V617F mutation greater than 95% of cases, whereas the remainder has a JAK2 exon 12 mutations. High hemoglobin or hematocrit counts are required, as is a bone marrow examination showing "prominent erythroid, granulocytic and megakaryocytic proliferation with pleomorphic, mature megakaryocytes."

Prefibrotic/early primary myelofibrosis edit

Prefibrotic primary myelofibrosis (Pre-PMF) is typically associated with JAK2, CALR, or MPL mutations and shows reticulin fibrosis no greater than grade 1. Anemia, splenomegaly, LDH above the upper limits and leukocytosis are minor criteria.[12]

Overtly fibrotic myelofibrosis edit

Like pre-PMF, overt primary myelofibrosis is associated with JAK2, CALR, or MPL mutations. However, a bone marrow biopsy will show reticulin and/or collagen fibrosis with a grade 2 or 3. Anemia, splenomegaly, LDH above the upper limits and leukocytosis are minor criteria.

MPN-U edit

Patients with otherwise unexplained thrombosis and with neoplasms that cannot be classified in one of the other categories.

Treatment edit

No curative drug treatment exists for MPNs.[13] Hematopoietic stem cell transplantation can be a curative treatment for a small group of patients, however MPN treatment is typically focused on symptom control and myelosuppressive drugs to help control the production of blood cells.[citation needed]

The goal of treatment for ET and PV is prevention of thrombohemorrhagic complications. The goal of treatment for MF is amelioration of anemia, splenomegaly, and other symptoms. Low-dose aspirin is effective in PV and ET. Tyrosine kinase inhibitors like imatinib have improved the prognosis of CML patients to near-normal life expectancy.[14]

Recently, a JAK2 inhibitor, namely ruxolitinib, has been approved for use in primary myelofibrosis.[15] Trials of these inhibitors are in progress for the treatment of the other myeloproliferative neoplasms.

Incidence edit

Although considered rare diseases, incidence rates of MPNs are increasing, in some cases tripling. It is hypothesized that the increase may be related to improved diagnostic abilities from the identification of the JAK2 and other gene markers, as well as continued refinement of the WHO guidelines.[16]

There is wide variation in reported MPN incidence and prevalence worldwide, with a publication bias suspected for essential thrombocythemia and primary myelofibrosis.[17]

History edit

The concept of myeloproliferative disease was first proposed in 1951 by the hematologist William Dameshek.[18] The discovery of the association of MPNs with the JAK2 gene marker in 2005 and the CALR marker in 2013 improved the ability to classify MPNs.[19]

MPNs were classified as blood cancers by the World Health Organization in 2008.[20] Previously, they were known as myeloproliferative diseases (MPD).

In 2016, Mastocytosis was no longer classified as an MPN.[21]

References edit

  1. ^ "Preventing Myelofibrosis from Progressing to Acute Myeloid Leukemia". Cure Today. Retrieved 2023-02-18.
  2. ^ . #MPNresearchFoundation. Archived from the original on 2020-07-11. Retrieved 2020-07-10.
  3. ^ Arber, Daniel A.; Orazi, Attilio; Hasserjian, Robert; Thiele, Jürgen; Borowitz, Michael J.; Le Beau, Michelle M.; Bloomfield, Clara D.; Cazzola, Mario; Vardiman, James W. (2016-05-19). "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia". Blood. 127 (20): 2391–2405. doi:10.1182/blood-2016-03-643544. ISSN 0006-4971. PMID 27069254.
  4. ^ Thapa B, Fazal S, Parsi M, Rogers H (2021). "Myeloproliferative Neoplasms". National Library of Medicine. StatPearls Publishing. PMID 30285359. Retrieved 8 July 2021.
  5. ^ Chia, Yuh Cai (2021). "Molecular Genetics of Thrombotic Myeloproliferative Neoplasms: Implications in Precision Oncology". Genes & Diseases. doi:10.1016/j.gendis.2021.01.002 – via Science Direct.
  6. ^ "Symptoms, Diagnosis, & Risk Factors | Seattle Cancer Care Alliance". www.seattlecca.org. Retrieved 2020-07-10.
  7. ^ Levene, Malcolm I.; Lewis, S. M.; Bain, Barbara J.; Imelda Bates (2001). Dacie & Lewis Practical Haematology. London: W B Saunders. p. 586. ISBN 0-443-06377-X.
  8. ^ Magor GW, Tallack MR, Klose NM, Taylor D, Korbie D, Mollee P, Trau M, Perkins AC (September 2016). "Rapid Molecular Profiling of Myeloproliferative Neoplasms Using Targeted Exon Resequencing of 86 Genes Involved in JAK-STAT Signaling and Epigenetic Regulation". The Journal of Molecular Diagnostics. 18 (5): 707–718. doi:10.1016/j.jmoldx.2016.05.006. PMID 27449473.
  9. ^ Barbui, Tiziano; Thiele, Jürgen; Gisslinger, Heinz; Kvasnicka, Hans Michael; Vannucchi, Alessandro M.; Guglielmelli, Paola; Orazi, Attilio; Tefferi, Ayalew (2018-02-09). "The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion". Blood Cancer Journal. 8 (2): 15. doi:10.1038/s41408-018-0054-y. ISSN 2044-5385. PMC 5807384. PMID 29426921.
  10. ^ Campbell PJ, Scott LM, Buck G, Wheatley K, East CL, Marsden JT, et al. (December 2005). "Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study". Lancet. 366 (9501): 1945–53. doi:10.1016/S0140-6736(05)67785-9. PMID 16325696. S2CID 36419846.
  11. ^ Beer PA, Campbell PJ, Scott LM, Bench AJ, Erber WN, Bareford D, et al. (July 2008). "MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort". Blood. 112 (1): 141–9. doi:10.1182/blood-2008-01-131664. PMID 18451306.
  12. ^ Mesa, Reuben. "What is Prefibrotic Primary Myelofibrosis?". Patient Power. HealthCentral LLC. Retrieved 23 June 2023.
  13. ^ . www.meduniwien.ac.at. Archived from the original on 2022-05-23. Retrieved 2020-07-09.
  14. ^ Tefferi, Ayalew; Vainchenker, William (2011-01-10). "Myeloproliferative Neoplasms: Molecular Pathophysiology, Essential Clinical Understanding, and Treatment Strategies". Journal of Clinical Oncology. 29 (5): 573–582. doi:10.1200/JCO.2010.29.8711. ISSN 0732-183X. PMID 21220604.
  15. ^ Tibes R, Bogenberger JM, Benson KL, Mesa RA (October 2012). "Current outlook on molecular pathogenesis and treatment of myeloproliferative neoplasms". Molecular Diagnosis & Therapy. 16 (5): 269–83. doi:10.1007/s40291-012-0006-3. PMID 23023734. S2CID 16010648.
  16. ^ Roaldsnes, Christina; Holst, René; Frederiksen, Henrik; Ghanima, Waleed (2017). "Myeloproliferative neoplasms: trends in incidence, prevalence and survival in Norway". European Journal of Haematology. 98 (1): 85–93. doi:10.1111/ejh.12788. ISSN 1600-0609. PMID 27500783. S2CID 19156436.
  17. ^ Titmarsh, Glen J.; Duncombe, Andrew S.; McMullin, Mary Frances; O'Rorke, Michael; Mesa, Ruben; De Vocht, Frank; Horan, Sarah; Fritschi, Lin; Clarke, Mike; Anderson, Lesley A. (June 2014). "How common are myeloproliferative neoplasms? A systematic review and meta-analysis". American Journal of Hematology. 89 (6): 581–587. doi:10.1002/ajh.23690. ISSN 1096-8652. PMID 24971434.
  18. ^ Dameshek W (April 1951). "Some speculations on the myeloproliferative syndromes". Blood. 6 (4): 372–5. doi:10.1182/blood.V6.4.372.372. PMID 14820991.
  19. ^ "Understanding MPNs- Overview | MPNRF". #MPNresearchFoundation. Retrieved 2020-07-10.
  20. ^ "Myeloproliferative Neoplasms". Cancer Support Community.
  21. ^ Barbui T, Thiele J, Gisslinger H, Kvasnicka HM, Vannucchi AM, Guglielmelli P, et al. (February 2018). "The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion". Blood Cancer Journal. 8 (2): 15. doi:10.1038/s41408-018-0054-y. PMC 5807384. PMID 29426921.

External links edit

  • Myeloproliferative+Disorders at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
  • MPN Info via Cancer.gov

December 01, 2023
myeloproliferative, neoplasm, mpns, group, rare, blood, cancers, which, excess, blood, cells, white, blood, cells, platelets, produced, bone, marrow, myelo, refers, bone, marrow, proliferative, describes, rapid, growth, blood, cells, neoplasm, describes, that,. Myeloproliferative neoplasms MPNs are a group of rare blood cancers in which excess red blood cells white blood cells or platelets are produced in the bone marrow Myelo refers to the bone marrow proliferative describes the rapid growth of blood cells and neoplasm describes that growth as abnormal and uncontrolled Myeloproliferative neoplasmOther namesMyeloproliferative diseases MPDs Myelogram of someone with a myeloproliferative disorder SpecialtyHematology and oncologyThe overproduction of blood cells is often associated with a somatic mutation for example in the JAK2 CALR TET2 and MPL gene markers In rare cases some MPNs such as primary myelofibrosis may accelerate and turn into acute myeloid leukemia 1 Contents 1 Classification 2 Causes 3 Diagnosis 3 1 Chronic myeloid leukemia 3 2 Chronic neutrophilic leukemia 3 3 Essential thrombocythemia 3 4 Polycythemia vera 3 5 Prefibrotic early primary myelofibrosis 3 6 Overtly fibrotic myelofibrosis 3 7 MPN U 4 Treatment 5 Incidence 6 History 7 References 8 External linksClassification editMPNs are classified as blood cancers by most institutions and organizations 2 In MPNs the neoplasm abnormal growth starts out as benign and can later become malignant As of 2016 the World Health Organization lists the following subcategories of MPNs 3 Chronic myeloid leukemia CML Chronic neutrophilic leukemia CNL Polycythemia vera PV Primary myelofibrosis PMF PMF Prefibrotic Stage PMF Overt Fibrotic Stage Essential thrombocythemia ET Chronic eosinophilic leukemia not otherwise specified MPN unclassifiable MPN U Causes editMPNs arise when precursor cells blast cells of the myeloid lineages in the bone marrow develop somatic mutations which cause them to grow abnormally There is a similar category of disease for the lymphoid lineage the lymphoproliferative disorders acute lymphoblastic leukemia lymphomas chronic lymphocytic leukemia and multiple myeloma 4 Genetics is believed to play a central role in the development of MPNs specially in developing thromboembolic and bleeding complications 5 Diagnosis editPeople with MPNs might not have symptoms when their disease is first detected via blood tests 6 Depending on the nature of the myeloproliferative neoplasm diagnostic tests may include red cell mass determination for polycythemia bone marrow aspirate and trephine biopsy arterial oxygen saturation and carboxyhaemoglobin level neutrophil alkaline phosphatase level vitamin B12 or B12 binding capacity serum urate 7 or direct sequencing of the patient s DNA 8 According to WHO diagnostic criteria published in 2016 myeloproliferative neoplasms are diagnosed as follows 9 Chronic myeloid leukemia edit Chronic myeloid leukemia CML has a presence of the hallmark Philadelphia Chromosome BCR ABL1 mutation Chronic neutrophilic leukemia edit Chronic neutrophilic leukemia CNL is characterized by a mutation in the CSF3R gene and an exclusion of other causes of neutrophilia Essential thrombocythemia edit Essential thrombocythemia ET is diagnosed with a platelet count greater than 450 109 L and is associated with the JAK2 V617F mutation in up to 55 of cases 10 and with an MPL thrombopoietin receptor mutation in up to 5 of cases 11 There should be no increase in reticulin fibers and the patient should not meet the criteria for other MPNs in particular Pre PMF Polycythemia vera edit Polycythemia vera PV is associated most often with the JAK2 V617F mutation greater than 95 of cases whereas the remainder has a JAK2 exon 12 mutations High hemoglobin or hematocrit counts are required as is a bone marrow examination showing prominent erythroid granulocytic and megakaryocytic proliferation with pleomorphic mature megakaryocytes Prefibrotic early primary myelofibrosis edit Prefibrotic primary myelofibrosis Pre PMF is typically associated with JAK2 CALR or MPL mutations and shows reticulin fibrosis no greater than grade 1 Anemia splenomegaly LDH above the upper limits and leukocytosis are minor criteria 12 Overtly fibrotic myelofibrosis edit Like pre PMF overt primary myelofibrosis is associated with JAK2 CALR or MPL mutations However a bone marrow biopsy will show reticulin and or collagen fibrosis with a grade 2 or 3 Anemia splenomegaly LDH above the upper limits and leukocytosis are minor criteria MPN U edit Patients with otherwise unexplained thrombosis and with neoplasms that cannot be classified in one of the other categories Treatment editNo curative drug treatment exists for MPNs 13 Hematopoietic stem cell transplantation can be a curative treatment for a small group of patients however MPN treatment is typically focused on symptom control and myelosuppressive drugs to help control the production of blood cells citation needed The goal of treatment for ET and PV is prevention of thrombohemorrhagic complications The goal of treatment for MF is amelioration of anemia splenomegaly and other symptoms Low dose aspirin is effective in PV and ET Tyrosine kinase inhibitors like imatinib have improved the prognosis of CML patients to near normal life expectancy 14 Recently a JAK2 inhibitor namely ruxolitinib has been approved for use in primary myelofibrosis 15 Trials of these inhibitors are in progress for the treatment of the other myeloproliferative neoplasms Incidence editAlthough considered rare diseases incidence rates of MPNs are increasing in some cases tripling It is hypothesized that the increase may be related to improved diagnostic abilities from the identification of the JAK2 and other gene markers as well as continued refinement of the WHO guidelines 16 There is wide variation in reported MPN incidence and prevalence worldwide with a publication bias suspected for essential thrombocythemia and primary myelofibrosis 17 History editThe concept of myeloproliferative disease was first proposed in 1951 by the hematologist William Dameshek 18 The discovery of the association of MPNs with the JAK2 gene marker in 2005 and the CALR marker in 2013 improved the ability to classify MPNs 19 MPNs were classified as blood cancers by the World Health Organization in 2008 20 Previously they were known as myeloproliferative diseases MPD In 2016 Mastocytosis was no longer classified as an MPN 21 References edit Preventing Myelofibrosis from Progressing to Acute Myeloid Leukemia Cure Today Retrieved 2023 02 18 Are Myeloproliferative Neoplasms MPNs Cancer MPNresearchFoundation Archived from the original on 2020 07 11 Retrieved 2020 07 10 Arber Daniel A Orazi Attilio Hasserjian Robert Thiele Jurgen Borowitz Michael J Le Beau Michelle M Bloomfield Clara D Cazzola Mario Vardiman James W 2016 05 19 The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia Blood 127 20 2391 2405 doi 10 1182 blood 2016 03 643544 ISSN 0006 4971 PMID 27069254 Thapa B Fazal S Parsi M Rogers H 2021 Myeloproliferative Neoplasms National Library of Medicine StatPearls Publishing PMID 30285359 Retrieved 8 July 2021 Chia Yuh Cai 2021 Molecular Genetics of Thrombotic Myeloproliferative Neoplasms Implications in Precision Oncology Genes amp Diseases doi 10 1016 j gendis 2021 01 002 via Science Direct Symptoms Diagnosis amp Risk Factors Seattle Cancer Care Alliance www seattlecca org Retrieved 2020 07 10 Levene Malcolm I Lewis S M Bain Barbara J Imelda Bates 2001 Dacie amp Lewis Practical Haematology London W B Saunders p 586 ISBN 0 443 06377 X Magor GW Tallack MR Klose NM Taylor D Korbie D Mollee P Trau M Perkins AC September 2016 Rapid Molecular Profiling of Myeloproliferative Neoplasms Using Targeted Exon Resequencing of 86 Genes Involved in JAK STAT Signaling and Epigenetic Regulation The Journal of Molecular Diagnostics 18 5 707 718 doi 10 1016 j jmoldx 2016 05 006 PMID 27449473 Barbui Tiziano Thiele Jurgen Gisslinger Heinz Kvasnicka Hans Michael Vannucchi Alessandro M Guglielmelli Paola Orazi Attilio Tefferi Ayalew 2018 02 09 The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms document summary and in depth discussion Blood Cancer Journal 8 2 15 doi 10 1038 s41408 018 0054 y ISSN 2044 5385 PMC 5807384 PMID 29426921 Campbell PJ Scott LM Buck G Wheatley K East CL Marsden JT et al December 2005 Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status a prospective study Lancet 366 9501 1945 53 doi 10 1016 S0140 6736 05 67785 9 PMID 16325696 S2CID 36419846 Beer PA Campbell PJ Scott LM Bench AJ Erber WN Bareford D et al July 2008 MPL mutations in myeloproliferative disorders analysis of the PT 1 cohort Blood 112 1 141 9 doi 10 1182 blood 2008 01 131664 PMID 18451306 Mesa Reuben What is Prefibrotic Primary Myelofibrosis Patient Power HealthCentral LLC Retrieved 23 June 2023 Summary www meduniwien ac at Archived from the original on 2022 05 23 Retrieved 2020 07 09 Tefferi Ayalew Vainchenker William 2011 01 10 Myeloproliferative Neoplasms Molecular Pathophysiology Essential Clinical Understanding and Treatment Strategies Journal of Clinical Oncology 29 5 573 582 doi 10 1200 JCO 2010 29 8711 ISSN 0732 183X PMID 21220604 Tibes R Bogenberger JM Benson KL Mesa RA October 2012 Current outlook on molecular pathogenesis and treatment of myeloproliferative neoplasms Molecular Diagnosis amp Therapy 16 5 269 83 doi 10 1007 s40291 012 0006 3 PMID 23023734 S2CID 16010648 Roaldsnes Christina Holst Rene Frederiksen Henrik Ghanima Waleed 2017 Myeloproliferative neoplasms trends in incidence prevalence and survival in Norway European Journal of Haematology 98 1 85 93 doi 10 1111 ejh 12788 ISSN 1600 0609 PMID 27500783 S2CID 19156436 Titmarsh Glen J Duncombe Andrew S McMullin Mary Frances O Rorke Michael Mesa Ruben De Vocht Frank Horan Sarah Fritschi Lin Clarke Mike Anderson Lesley A June 2014 How common are myeloproliferative neoplasms A systematic review and meta analysis American Journal of Hematology 89 6 581 587 doi 10 1002 ajh 23690 ISSN 1096 8652 PMID 24971434 Dameshek W April 1951 Some speculations on the myeloproliferative syndromes Blood 6 4 372 5 doi 10 1182 blood V6 4 372 372 PMID 14820991 Understanding MPNs Overview MPNRF MPNresearchFoundation Retrieved 2020 07 10 Myeloproliferative Neoplasms Cancer Support Community Barbui T Thiele J Gisslinger H Kvasnicka HM Vannucchi AM Guglielmelli P et al February 2018 The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms document summary and in depth discussion Blood Cancer Journal 8 2 15 doi 10 1038 s41408 018 0054 y PMC 5807384 PMID 29426921 External links editMyeloproliferative Disorders at the U S National Library of Medicine Medical Subject Headings MeSH MPN Info via Cancer gov Retrieved from https en wikipedia org w index php title Myeloproliferative neoplasm amp oldid 1178795039, wikipedia, wiki, book, books, library,

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