Myeloproliferative Disease Clinical Presentation

  • Author: Haleem J Rasool, MD, FACP; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Nov 17, 2011
 

History

  • Easy fatigability
  • Anorexia, weight loss
  • Abdominal discomfort and early satiety secondary to splenomegaly is more common in chronic myelogenous leukemia and agnogenic myeloid metaplasia (see example below).Peripheral smear of a patient with agnogenic myeloPeripheral smear of a patient with agnogenic myeloid metaplasia (myelofibrosis) shows leukoerythroblastosis. This photomicrograph also shows giant platelets.
  • Easy bruising, bleeding, and/or symptoms of thrombosis
  • Swollen, painful joint(s) secondary to gouty arthritis secondary to hyperuricemia
  • Priapism, tinnitus, or stupor from leukostasis
  • Left upper quadrant and left shoulder pain as a consequence of splenic infarction and perisplenitis
  • In many patients, abnormal blood counts are noted on a blood test performed for other reasons.
  • A study by Scherber et al assessed the use of an 18-item assessment form called the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), which is designed to assess symptoms of myelofibrosis, essential thrombocythemia, and polycythemia vera. The study found that the MPN-SAF is a comprehensive and reliable instrument that correlated well with physicians’ blinded opinion of patient symptoms.[6]
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Physical

  • Pallor, except in patients with polycythemia vera
  • Plethora secondary to polycythemia
  • Petechiae and/or ecchymosis
  • Palpable spleen and/or liver
  • Occasionally, syndrome of fever accompanied by painful maculopapular violaceous lesions on trunk, arms, legs, and face, which is called acute febrile neutrophilic dermatosis or Sweet syndrome
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Causes

As with other malignant disorders, the precise cause of myeloproliferative disease is unknown. The etiology is complex, incompletely understood, and likely a multistep process involving more than one gene.

Philadelphia chromosome, t(9:22), is found in most patients who have chronic myelogenous leukemia. Even when the Philadelphia chromosome is negative, the gene bcr-abl, formed as result of t(9:22), tests positive in patients with chronic myelogenous leukemia using molecular techniques. Bcr-abl encodes a fusion protein with tyrosine kinase activity, which is constitutively expressed and is regarded as the central mechanism that underlies the chronic phase of chronic myelogenous leukemia.[7]

In a retrospective study of 11,000 patients in Sweden with myeloproliferative neoplasm, the authors reviewed the incidence of acute myeloid leukemia (AML) and myelodysplastic syndrome that were secondary to treatment; the study found that treatment with radioactive phosphorous but not hydroxyurea increased the risk of myelodysplastic syndrome and AML.[8]

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Contributor Information and Disclosures
Author

Haleem J Rasool, MD, FACP  Hematologist/Oncologist, Department of Oncology, Franciscan Skemp Healthcare

Haleem J Rasool, MD, FACP is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine and American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Koyamangalath Krishnan, MD, FRCP, FACP  Paul Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine and Chief of Hematology-Oncology, James H Quillen College of Medicine at East Tennessee State University

Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, and Royal College of Physicians

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Troy H Guthrie, Jr, MD  Director of Cancer Institute, Baptist Medical Center

Troy H Guthrie, Jr, MD is a member of the following medical societies: American Federation for Medical Research, American Medical Association, American Society of Hematology, Florida Medical Association, Medical Association of Georgia, and Southern Medical Association

Disclosure: Nothing to disclose.

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

References

  1. Vardiman JW. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002;100:2299-2300. [Medline]. [Full Text].

  2. Baxter EJ, Scott LM, Campbell PJ. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. Mar 19-25 2005;365(9464):1054-61. [Medline].

  3. James C, Ugo V, Le Couedic JP. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. Apr 28 2005;434(7037):1144-8. [Medline].

  4. Mesa RA, Powell H, Lasho T, Dewald G, McClure R, Tefferi A. JAK2(V617) and leukemic transformation in myelofirbrosis with myeloid metaplasia. Leuk Res. 2006/11;30 (11):1457-60.

  5. Anand S, Stedham F, Beer P, et al. Effects of the JAK2 mutation on the hematopoietic stem and progenitor compartment in human myeloproliferative neoplasms. Blood. Jul 7 2011;118(1):177-81. [Medline].

  6. Scherber R, Dueck AC, Johansson P, et al. The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF): international prospective validation and reliability trial in 402 patients. Blood. Jul 14 2011;118(2):401-8. [Medline].

  7. Donato NJ, Talpaz M. Clinical use of tyrosine kinase inhibitors: therapy for chronic myelogenous leukemia and other cancers. Clin Cancer Res. Aug 2000;6(8):2965-6. [Medline].

  8. Bjorkholm M, Derolf AR, Hultcrantz M, et al. Treatment-related risk factors for transformation to acute myeloid leukemia and myelodysplastic syndromes in myeloproliferative neoplasms. J Clin Oncol. Jun 10 2011;29(17):2410-5. [Medline]. [Full Text].

  9. O'Brien SG, Guilhot F, Larson RA. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. Mar 13 2003;348(11):994-1004. [Medline].

  10. Kaplan ME, Mack K, Goldberg JD. Long-term management of polycythemia vera with hydroxyurea: a progress report. Semin Hematol. Jul 1986;23(3):167-71. [Medline].

  11. Doll DC, Gabrail NY, List AF. Introduction: myeloproliferative disorders. Semin Oncol. Aug 1995;22(4):305-6. [Medline].

  12. Faderl S, Kantarjian HM, Talpaz M. New treatment approaches for chronic myelogenous leukemia. Semin Oncol. Oct 2000;27(5):578-86. [Medline].

  13. Froom P, Elmalah I, Braester A. Clodronate in myelofibrosis: a case report. Am J Med Sci. Feb 2002;323(2):115-6. [Medline].

  14. Johansson P, Kutti J, Andreasson B. Trends in the incidence of chronic Philadelphia chromosome negative (Ph-) myeloproliferative disorders in the city of Goteborg, Sweden, during 1983-99. J Intern Med. Aug 2004;256(2):161-5.

  15. Kralovics R, Passamonti F, Buser AS. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. Apr 28 2005;352(17):1779-90. [Medline].

  16. Kutti J, Ridell B. Epidemiology of the myeloproliferative disorders: essential thrombocythaemia, polycythaemia vera and idiopathic myelofibrosis. Pathol Biol (Paris). Mar 2001;49(2):164-6. [Medline].

  17. Levine RL, Wadleigh M, Cools J. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. Apr 2005;7(4):387-97. [Medline].

  18. O'Brien S, Tefferi A, Valent P. Chronic myelogenous leukemia and myeloproliferative disease. Hematology (Am Soc Hematol Educ Program). 2004;146-62.

  19. Pardanani A, Brockman SR, Paternoster SF. FIP1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosinophilia. Blood. Nov 15 2004;104(10):3038-45. [Medline]. [Full Text].

  20. Staerk J, Kallin A, Demoulin JB. JAK1 and Tyk2 Activation by the Homologous Polycythemia Vera JAK2 V617F Mutation:CROSS-TALK WITH IGF1 RECEPTOR. J Biol Chem. Dec 23 2005;280(51):41893-9.

  21. Tefferi A, Solberg LA, Silverstein MN. A clinical update in polycythemia vera and essential thrombocythemia. Am J Med. Aug 1 2000;109(2):141-9. [Medline].

 
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Peripheral smear of a patient with chronic myelogenous leukemia (CML) shows leukocytosis with extreme left shift and basophilia.
Peripheral smear of a patient with chronic myelogenous leukemia (CML) in blastic phase shows several blasts.
Peripheral smear of a patient with essential thrombocythemia (ET) shows markedly increased number of platelets. Some of the platelets are giant (arrow).
Peripheral smear of a patient with agnogenic myeloid metaplasia (myelofibrosis) shows leukoerythroblastosis. This photomicrograph also shows giant platelets.
Photomicrograph of a peripheral smear of a patient with agnogenic myeloid metaplasia (myelofibrosis) shows findings of leukoerythroblastosis, giant platelets, and few teardrop cells.
Table. Comparison of FAB and WHO Classifications of Chronic Myeloproliferative Diseases.
FAB WHO
Chronic myelogenous leukemiaChronic myelogenous leukemia
Polycythemia veraPolycythemia vera
Essential thrombocythemiaEssential thrombocythemia
Agnogenic myeloid metaplasia/myelofibrosisChronic idiopathic myelofibrosis
...Chronic neutrophilic leukemia
...Chronic eosinophilic leukemia/hypereosinophilic syndrome
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