Abnormalities of chromosome 12p 13 and malignant proliferation of eosinophils: a nonrandom association

Abstract

Four patients representing a spectrum of haematological malignancies are reported. Two patients had Philadelphia chromosome negative myeloproliferative disorders, one had acute lymphoblastic leukaemia and one had eosinophilic leukaemia. In each case eosinophilia was present and demonstrated to be part of the malignancy by the association of clonally abnormal metaphases with eosinophil granules. Abnormalities involving the short arm of chromosome 12 (12p13) were a constant feature in all four cases and therefore a nonrandom association between this chromosome region and malignant eosinophil proliferation is proposed.

Protein tyrosine phosphatase containing SH2 domains: characterization, preferential expression in hematopoietic cells, and localization to human chromosome 12p12-p13.

“…Less commonly involved rearrangements involve dic(12;17)(pll;p12) and t(12;13)(p13;q14). Abnormalities of chromosome 12pl3 have also been associated with malignant proliferation of eosinophils (26). Experiments are in progress to assess the role of HCP in cases of ALL with rearrangements of 12p12-p13.…”

The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes

“…Rearrangements of PDGFRB at chromosome band 5q33 were first recognized in cases variably reported as chronic myelomonocytic leukemia (CMML) with eosinophilia, or less commonly, as CEL. [38][39][40][41] More recently, the gene that encodes the alpha chain of PDGFR, PDGFRA, located at chromosome band 4q12, was found to be involved in cryptic translocations in cases of CEL and in a substantial number of cases reported as idiopathic hypereosinophilic syndrome. 7 Rearrangements of FGFR1 have also been implicated in myeloproliferations with prominent eosinophilia, that is, the "8p11.2 myeloproliferative syndrome."…”

Recent advances in pathogenesis and management of hypereosinophilic syndromes

“…Existence of a true MP disorder in a subgroup of IHES patients remained purely speculative at the time, as initial investigators were unable to detect a clonal myeloid disorder responsible for eosinophilic expansion. Demonstration of eosinophil clonality has proven difficult, with only a few reports showing chromosomal abnormalities adjacent to eosinophil granules (13) or skewed methylation patterns of X-linked genes such as phosphoglycerate kinase (PGK) (14) and human androgen receptor (HU-MARA) (15) in purified granulocytes and eosinophils, respectively. In practice, these methods are rarely applicable in IHES patients, as karyotype abnormalities are rare in this disorder, and X-linked polymorphisms can be investigated only in female patients, in the setting of a disease that predominantly affects males.…”