General Information About Myelodysplastic/ Myeloproliferative Neoplasms
The myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are clonal myeloid disorders that possess both dysplastic and proliferative features but are not properly classified as either myelodysplastic syndromes (MDS) or chronic myeloproliferative disorders (CMPD). This category is composed of three major myeloid disorders: chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), and atypical chronic myeloid leukemia (aCML). Myeloid disease that shows features of both MDS and CMPD but does not meet the criteria for any of the three major MDS/MPN entities is designated as myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN-UC).
The French-American-British classification scheme for myeloid disorders did not contain this overlap category, which made the classification of CMML particularly difficult.[2,3] Recognizing the special diagnostic challenge that these diseases represent, a group of pathologists and clinicians sponsored by the World Health Organization (WHO) created the MDS/MPN category to provide a less restrictive view of myeloid disorders, which in some instances clearly overlap. The WHO group proposed that the new MDS/MPN category would allow for more focused clinical and laboratory investigations of myeloid proliferation, abnormal proliferation, and dysplasia.[1,4]
The etiology of MDS/ MPN is not known. The incidence of MDS/MPN varies widely, ranging from approximately 3 per 100,000 individuals older than 60 years annually for CMML to as few as 0.13 per 100,000 children from birth to 14 years annually for JMML. Reliable data concerning the incidence of aCML, a recently defined entity, are not available. The incidence of MDS/MPN-UC is unknown.
The pathophysiology of MDS/MPN involves abnormalities in the regulation of myeloid pathways for cellular proliferation, maturation, and survival. Clinical symptoms are caused by complications resulting from the following:
- Dysplastic cells that function abnormally.
- Leukemic infiltration of various organ systems.
- General constitutional symptoms, such as fever and malaise. (Refer to the PDQ summary on Fever, Sweats, and Hot Flashes for more information on fever.)
Patients with MDS/MPN do not have a Philadelphia chromosome or BCR/ABL fusion gene. No specific genetic defects have been identified for any of these entities, though abnormalities in regulation of the ras pathway of signaling proteins appears to be a common finding in CMML, aCML, and JMML and may have some role in the abnormal myeloid proliferation associated with these diseases. In general, treatment of these diseases is tailored to the manifestations, myeloproliferative or myelodysplastic, that predominate in the individual patient.References
- Vardiman JW, Harris NL, Brunning RD: The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 100 (7): 2292-302, 2002. [PUBMED Abstract]
- Germing U, Gattermann N, Minning H, et al.: Problems in the classification of CMML--dysplastic versus proliferative type. Leuk Res 22 (10): 871-8, 1998. [PUBMED Abstract]
- Voglová J, Chrobák L, Neuwirtová R, et al.: Myelodysplastic and myeloproliferative type of chronic myelomonocytic leukemia--distinct subgroups or two stages of the same disease? Leuk Res 25 (6): 493-9, 2001. [PUBMED Abstract]
- Vardiman JW: Myelodysplastic/myeloproliferative diseases: introduction. In: Jaffe ES, Harris NL, Stein H, et al., eds.: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press, 2001. World Health Organization Classification of Tumours, 3, pp 47-8.
- Bain BJ: The relationship between the myelodysplastic syndromes and the myeloproliferative disorders. Leuk Lymphoma 34 (5-6): 443-9, 1999. [PUBMED Abstract]