Complete and long-lasting cytologic and molecular remission of FIP1L1-PDGFRA-positive acute eosinophil myeloid leukaemia, treated with low-dose imatinib monotherapy.

Myeloproliferative neoplasms associated with FIP1L1-PDGFR rearrangements represent a rare subset of myeloid and lymphoid malignancies, characterised by the presence of eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1 genes. The fusion product of such genes is a tyrosine kinase oncoprotein sensitive to imatinib, which to date results to be the standard of care for FIP1L1-PDGFRA-positive chronic myeloproliferative disorders with eosinophilia. However, the coexistence of FIP1L1-PDGFRA rearrangement associated with acute myeloid leukaemia is extremely rare. Here, we report a rare case of FIP1L1-PDGFRA-positive acute myeloid leukaemia, with marked peripheral blood and bone marrow eosinophilia, treated with low dose of imatinib monotherapy, achieving a rapid and long-lasting complete cytologic and molecular remission, without need for intensive chemotherapy.

A case of acute eosinophilic granulocytic leukemia with PML-RAR alpha fusion gene expression and response to all-trans retinoic acid.

A typical case of eosinophilic granulocytic leukemia with PML-RAR alpha fusion gene expression is reported. The patient achieved complete remission after oral administration of all-trans retinoic acid without any exposure to cytotoxic agents. The facts strongly suggest that the genetic event occurred at the level of pluripotent stem cells.

Optimized conditions for gene transfection into the human eosinophilic cell line EoL-1 by electroporation.

Eosinophils are emerging as an increasingly important cell in the immunoregulatory network of normal and pathological processes. No studies has yet described optimized experimental strategies to transfect DNA into human eosinophils. Using a frequently employed in vitro model of human eosinophil, the EoL-1 cells, we now described the optimal transfection of DNA into these cells by electroporation. Our results indicate that electroporation can efficiently and reproducibly transfect DNA into EoL-1 cells. Optimal electroporation conditions consist of the use of 1 X RPMI medium 1640 with 10% FBS, voltage setting at 275 V, 1150 microF capacitance, 40 mg of DNA and 4.0 X 10(7) cells/ml per electroporation in a total volume of 0.5 ml in 0.4 cm gap cuvettes. These conditions may be a useful protocol for transfecting eosinophil cell lines.

Acute myelogenous leukemia with eosinophilic differentiation and trisomy-1.

A 50-year-old woman presented with anemia and eosinophilia. Her bone marrow biopsy, peripheral blood, and clinical features were consistent with a diagnosis of an evolving acute myelogenous leukemia. Striking dysplastic eosinophilic differentiation associated with trisomy-1 was evident, and eosinophil granule major basic protein was detected in involved tissue. Trisomy-1 has not been previously reported in association with acute myelogenous leukemia showing eosinophilic differentiation. Intensive cytotoxic chemotherapy produced a short-lived clinical and cytogenetic remission. At autopsy multiple tumor nodules composed of dysplastic eosinophil precursors and myeloblasts were evident in multiple organs.

Eosinophilic leukaemia with trisomy 8 and double gammopathy.

Prolonged eosinophilia of unknown cause has generally been described as the hypereosinophilic syndrome, and is characterised by peripheral blood and bone marrow infiltration and frequent multisystem disease. The nature of this disorder has been questioned, and the clinical features are quite variable, suggesting its heterogeneity and probable neoplastic aetiology. A patient with severe eosinophilia, karyotype abnormalities, serum gammopathy and massive organ disease is reported. The clinical course was aggressive despite cytoreduction of eosinophils and terminated in multisystem failure. These findings are consistent with a diagnosis of eosinophilic leukaemia, and it is suggested that chromosome and cell culture studies might be useful in the early diagnosis of this controversial entity.

CALM-AF10 fusion gene in leukemias: simple and inversion-associated translocation (10;11).

A translocation (10;11)(p12;q14) was observed in two children, one with acute eosinophilic leukemia and the other with acute T-cell lymphoblastic leukemia. The presence of CALM-AF10 fusion was ascertained by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Fluorescence in situ hybridization (FISH) analysis showed that AF10 gene splitting was associated with partial inversion of chromosome 11 in the first patient. In addition, FISH analysis also determined the orientation of the CALM gene, 5' telomere to 3' centromere on 11q.

The eosinophilic variant of acute myelomonocytic leukemia developing as a secondary leukemia in a patient with mycosis fungoides.

The eosinophilic variant of acute myelomonocytic leukemia (AMML) is highly associated with characteristic abnormalities of chromosome 16. Leukemias developing secondary to chemotherapy frequently show abnormalities of chromosomes 5 and 7. This report describes a secondary AMML, eosinophilic variant (M4Eo), developing in a patient with coexistent mycosis fungoides who had received chemotherapy, including an alkylating agent, and showing characteristic abnormalities of both chromosomes 7 and 16. This is the first reported case of the M4Eo arising secondarily in a patient treated for another hematopoietic malignancy, and the second case of treatment-induced M4Eo to show coexistent abnormalities of chromosomes 7 and 16. Additional cytochemical, ultrastructural, and cell surface marker findings are described supporting malignant transformation of the eosinophilic cell line.

Differential and constitutive expression of the DRB1 and DRA gene products controls the surface HLA-DR expression level in human eosinophilic leukaemia cell lines.

Use of 2-D gel and imaging plate analysis enabled biosynthetically radiolabeled immunoprecipitates to be quantitated at the very low level of gene products during processing from RER inside cells to cell surface. We used this efficient and sensitive measurement to analyse expression of HLA-DR molecules in human eosinophilic leukaemia cell lines. We found that they synthesized a constitutive amount of DRA gene products and differential amounts of DRB1 gene products. Thus, the incompletely inducible expression of DRB1 gene products was responsible for the limited accumulation of normally assembled molecules for cell surface expression and the lack of serological determination.

Distinction of eosinophilic leukaemia from idiopathic hypereosinophilic syndrome by analysis of Wilms' tumour gene expression.

In patients presenting with immature eosinophilic precursors it is notoriously difficult to distinguish acute eosinophilic leukaemia (EoL) from the benign idiopathic hypereosinophilic syndrome (HES), based on morphological, cytochemical and immunophenotyping criteria, alone. Cytogenetic analysis or fluorescence in situ hybridization (FISH) can help in discriminating between these rare haematological disorders, but often treatment decisions cannot wait for the results of these time-consuming techniques. Recently, we and others found Wilms' tumour (WT1) gene expression to be increased in virtually all patients with acute leukaemias, whereas normal haemopoietic progenitors express the WT1 gene at much lower levels or not at all. To determine whether detection of WT1 gene expression is useful to distinguish EoL from HES patients, we analysed, by RT-PCR, bone marrow or blood mononuclear cells from EoL (n=3), HES (n=3) and reactive eosinophilia patients (n = 4) for WT1 gene expression. Using our WT1-RT-PCR protocol, we found WT1 gene expression to be restricted to EoL patients. By detecting WT1 mRNA transcripts in the cerebrospinal fluid using RT-PCR, we were also able to diagnose isolated CNS-relapsed leukaemia, initially confused with bacterial meningitis, in an EoL patient. In conclusion, we show that WT1-RT-PCR is a powerful complementary diagnostic tool to distinguish acute eosinophilic leukaemia from the hypereosinophilic syndromes. This observation needs confirmation in a larger series of EoL and HES patients.

Acute eosinophilic leukemia in a patient with preexistent myelodysplastic syndrome.

A case of acute eosinophilic leukemia (EoL) that occurred in a patient with preexistent myelodysplastic syndrome is reported. The patient was initially diagnosed as having refractory anemia (RA) on the basis of pancytopenia with dysplasia and chromosomal abnormalities. Two years later, he was readmitted because of progression of pancytopenia, and bone marrow and peripheral blood showed immature dysplastic eosinophils. Clonal assay of peripheral blood mononuclear cells revealed autonomous growth of colony-forming unit eosinophils. Cytotoxic chemotherapy did not induce remission, and extensive myelofibrosis developed. Cytogenetic analysis in the RA state showed +1p- and -7 whereas complicated abnormalities including +1p-, 3q- and 7p- dominated in the EoL state.