Simona Aschero

MET dysregulation is a hallmark of aggressive disease in multiple myeloma patients

Abnormal activation of MET/HGF (Hepatocyte Growth Factor) pathway has been described in several tumours and increased HGF plasmatic levels have been detected in patients with aggressive multiple myeloma (MM). MET and HGF mRNA expression was investigated in 105 samples of purified plasma cells derived from newly diagnosed MM patients treated with bortezomib‐based induction therapy. Gene expression was compared with response to therapy and clinical outcome. MET gene copy number was also evaluated. MET mRNA expression was higher in CD138+ than in CD138− cells (median 76·90 vs. 11·24; P = 0·0009). Low MET mRNA expression characterized patients with better response (complete response or very good partial response) compared to other patients (median 56·10 vs. 134·83; P = 0·0006). After a median follow‐up of 50 months, patients with high MET mRNA expression displayed a worse progression‐free survival (PFS; P = 0·0029) and overall survival (OS; P = 0·0023) compared to those with low MET mRNA levels. Patients with both high MET mRNA expression and high β2‐microglobulin level (>5·5 mg/l) had further worse median PFS (P < 0·0001) and OS (P < 0·0001). Patients carrying 4 MET gene copies (8 out of 82, 9·8%) also had a short PFS. High MET mRNA expression identifies patients with dismal PFS and OS and the combination with high β2‐microglobulin further characterizes patients with worse outcome.

Chromosome 1 abnormalities in elderly patients with newly diagnosed multiple myeloma treated with novel therapies.

Multiple myeloma is a plasma cell disorder characterized by malignant plasma cell infiltration in the bone marrow, serum and/or urine monoclonal protein and organ damage. The aim of this study was to investigate the impact of chromosome 1 abnormalities in a group of elderly patients (>65 years) with newly diagnosed multiple myeloma enrolled in the GIMEMA-MM-03-05 trial and treated with bortezomib, melphalan and prednisone or bortezomib, melphalan, prednisone and thalidomide followed by bortezomib and thalidomide maintenance. We also evaluated the link between chromosome 1 abnormalities and other clinical, genetic and immunophenotypic features by a multivariate logistic regression model. Interphase fluorescence in situ hybridization on immunomagnetically purified plasma cells and bone marrow multiparameter flow cytometry were employed. A multivariate Cox model showed that chromosome 1 abnormalities, age >75 years and a CD19+/CD117− immunophenotype of bone marrow plasma cells were independent risk factors for overall survival in elderly patients with newly diagnosed multiple myeloma. Moreover, a detrimental effect of thalidomide, even when administered in association with bortezomib, was observed in patients with abnormal chromosome 1 as well as in those with 17p deletion, while the benefit of adding thalidomide to the bortezomib-melphalan-prednisone regimen was noted in patients carrying an aggressive CD19+/CD117− bone marrow plasma cell immunophenotype. This trial was registered at www.clinicaltri-als.gov as #NCT01063179.

A complex karyotype including a t(2;11) in a paediatric ependymoma: case report and review of the literature

Ependymomas are glial tumours representing approximately 5–10% of all intracranial tumours and are the third most common primary brain tumour in childhood. Only a few karyotypic studies on paediatric ependymomas have been published and no specific chromosomal aberration has been specifically related to this type of cancer. We performed cytogenetic analysis of an ependymoma in an 11-year-old boy. Our patient showed a complex karyotype, characterized by a near-tetraploidy and a sole structural unbalanced aberration: der(2)t(2;11)(q11.2;q13.1), which has not been described before. We here discuss such cytogenetic findings, comparing our data with those reported in the literature.