Autoimmune hemolytic anemia (AIHA) is a rare and heterogeneous disease with a presentation/phenotype ranging from mild/compensated to life-threatening. 1,2 Moreover, some cases show refractoriness to/relapse after first and further therapy lines, leading to significant and underestimated healthcare burden. Here, we retrospectively analyzed 378 primary AIHA cases (135 M and 243 F, median age 61 years, range 5-94) from eight Italian hematological centers and fol-
Activation of telomerase reverse transcriptase (hTERT) is essential for unlimited cell growth and plays a critical role in tumorigenesis. We investigated hTERT gene expression in 134 B-cell chronic lymphocytic leukemia (B-CLL) cases and evaluated its prognostic value with other prognostic markers (IgVH mutation status, CD38 and ZAP-70 expression). Real-time PCR assays to quantify either all hTERT transcripts (AT) or only the full length (FL) transcript encoding the functional protein were developed. hTERT-AT levels strongly correlated with hTERT-FT levels (r ¼ 0.743, Po0.0001); both inversely correlated with the percentage of IgVH mutation (Po0.005) and were significantly higher in unmutated than in mutated cases (P ¼ 0.004 and P ¼ 0.001, respectively). The hTERT values which best discriminated between the unmutated and mutated IgVH cases were 150 and 40 copies for hTERT-AT and hTERT-FL, respectively. Using these cut-off values, there was a significant difference in the survival of patients with high or low hTERT levels (Po0.0001). Unmutated cases with low hTERT levels had an overall survival close to mutated cases with high hTERT levels. Thus, this work identifies hTERT-RNA level as a new prognostic marker in B-CLL, and may be used to identify previously unrecognized patient groups with the same IgVH mutation status and different disease outcomes. Leukemia (2007) 21, 965-972.
Chemokines and their receptors play a pivotal role in the regulation of B-lymphocyte trafficking. This study was aimed at investigating the pattern of chemokine receptor expression, including CCR1 to CCR3, CCR5 to CCR7, CXCR1 to CXCR5, and the migration ability of multiple myeloma (MM) plasma cells (PC). PC were recovered from the bone marrow (BM) of 29 MM patients, extramedullary sites of 10 patients and the BM of five controls. Flow cytometry analysis showed that the receptors mainly expressed on malignant BM PC were represented by CXCR4 (70% of patients), CCR1 (25%), CCR2 (25%), CCR5 (17%) and CXCR3 (20%), while other receptors were commonly lacking. The analysis performed on extramedullary (peripheral blood and pleural effusion) malignant PC demonstrated that the most represented receptors were CXCR4 (100%), CCR2 (66%) and CXCR1 (60%). The migratory capability of malignant PC at resting conditions identified three groups of patients with different migration (low, intermediate and high). As CXCR4 was the relevant chemokine receptor expressed by MM PC, its ligand CXCL12 induced their migration. These data suggest that malignant PC from MM display different chemokine receptor profiles and that CXCR4 is fully functional and might play a role in the spreading of the disease.
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