The chronic myeloproliferative disorders: clonality and clinical heterogeneity

Jerry L Spivak
Seminars in Hematology 2004, 41 (2 Suppl 3): 1-5
The chronic myeloproliferative disorders (MPD), polycythemia vera (PV), chronic idiopathic myelofibrosis (IMF), essential thrombocytosis (ET), and chronic myelogenous leukemia (CML), are thought to be clonal disorders arising in a multipotent hematopoietic progenitor cell. However, establishing the diagnosis of an MPD other than CML is problematic due to a lack of clinically applicable clonal markers. Furthermore, in some patients, in whom a classical MPD phenotype is present, the hematopoietic stem cells appear to be polyclonal, suggesting that the chronic MPD other than CML may actually be a genetically heterogeneous group of disorders. Furthermore, since the aberrant clone is believed to arise from a multipotent hematopoietic stem cell, the non-CML chronic MPD-ET, PV, and IMF-could be related. Additional unresolved issues regarding the MPD include: identification of the multipotent hematopoietic progenitor cell involved, the molecular basis for the clinical heterogeneity amongst the individual MPD, the clinical significance of clonality in non-CML MPD, and reconciliation of therapy with the clonal and clinical heterogeneity of these disorders. Determination of clonality has largely been carried out using X chromosome-linked polymorphisms, but such studies are limited to women and with increasing patient age are compromised by skewing of allelic expression in both neutrophils and T lymphocytes, making the results difficult to interpret. X chromosome-linked polymorphism studies have indicated that in PV the target stem cell is one that gives rise to both lymphoid and myeloid progenitors. Recently, two epigenetic markers have been identified in the MPD: impaired expression of the thrombopoietin receptor, Mpl, in platelets and megakaryocytes, and overexpression in neutrophils of the mRNA of a gene designated polycythemia rubra vera-1 (PRV-1). The role of these epigenetic abnormalities in the diagnosis of the MPD remains to be established. Currently, given the unresolved issues with respect to the clinical and clonal heterogeneity of the MPD, treatment needs to be tailored individually in patients with an MPD.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"