Chronic Eosinophilic Leukemia Hypereosinophilic Syndrome

Myeloproliferative hypereosinophilic diseases are defined by a persistent (>6 months) unexplained eosinophilia greater than 1.5 X 109/L, a hypercellular bone marrow with eosinophilia, and tissue damage. They are discriminated from idiopathic hypere-osinophilic syndrome by the presence of tissue damage, although this may indeed be artificial as tissue damage may be subclinical or occur in the future. While investigating these patients, a reactive cause of eosinophilia such as allergies, parasitic infections, and other malignancies (e.g., on detection of phenotypi-cally abnormal T lymphocytes56) should be assiduously excluded. Eosinophil morphology varies from normal to include abnormalities such as degranulation, cytoplasmic vacuolation, hypolobulation, or hyperlob-ulation. The presence of Chronic eosinophilic leukemia (CEL) is suggested by increased proportion of blasts, hepatosplenomegaly, raised serum tryptase, vitamin B12, and a cytogenetic abnormality. In some patients the diagnosis will only be apparent after transformation to acute myeloid leukemia.

The detection of cytogenetic abnormalities is useful in discriminating CEL from a reactive eosinophilia. Abnormalities involving 5q33 or 8p11 are most frequent and clonality has been demonstrated even in patients with normal cytogenetics by X-chromosome inactivation patterns.57 Abnormalities of 5q33, especially t(5;12)(q33;p13), produce the fusion oncogene TEL-PDGFRp with constitutive activation of the kinase domain of PDGFRp originally cloned by Golub.58 Variable morphological features have been described from chronic myelomonocytic leukemia (CMML)-like to atypical CML, as reviewed by Bain.59 Two other translocations involving the PDGFRfi gene are t(5;7)(q33;q11.2) and t(5;10) (q33;21.2). Rarer translocations associated with 8p11 involve the fibroblast growth factor receptor-1 (FGFR1) most commonly fusing with the ZNF198 gene of 13q12 generating t(8;13)(q11;q12); they are frequently associated with non-Hodgkin's lymphomas and have a particular tendency to leukemic transformation.60-63

Recently, a novel tyrosine kinase, FIP1L1-PDGFRa, has been described in 9/16 patients with hypere-osinophilic syndrome64 and 3/5 with systemic mastocy-tosis.65 This is generated by microdeletion of CHIC2 and is only detectable by RTPCR or FISH; conventional cytogenetics is unhelpful. Patients with FIP1L1-PDGFRa and eosinophilia have been reported to show a dramatic response to imatinib mesylate64,66 as have several with activated PDGFRB fusion tyrosine kinases.6768

Was this article helpful?

0 0
Allergy Relief

Allergy Relief

Have you ever wondered how to fight allergies? Here are some useful information on allergies and how to relief its effects. This is the most comprehensive report on allergy relief you will ever read.

Get My Free Ebook

Post a comment