Dual role of the CXCL12 polymorphism in patients with chronic lymphocytic leukemia.

The CXCL12 [chemokine (C-X-C motif) ligand 12] is a member of the CXC family of chemokines and interacts with its CXCR4 receptor. The CXCL12/CXCR4 axis is involved in regulation of proliferation, survival and trafficking of hematopoietic stem cells, including B lymphocytes and disruption within this signaling pathway has been implicated in pathogenesis of chronic lymphocytic leukemia (CLL). The aim of this study was to determine a potential association of the CXCL12 rs1801157 G > A polymorphism with susceptibility to CLL, the disease course and efficacy of therapy. Also, expression of the CD74 and CD38 proteins on B cells was analyzed in relation to clinical parameters and genotyping results. A total of 124 patients with CLL and 75 healthy controls were studied. CXCL12 genotyping was performed using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) method. The CD74 and CD38 surface expression was determined using flow cytometry. There was a significantly increased frequency of the A allele and AA genotype in CLL patients compared with control group (P < 0.001 in both cases). In addition, the A allele was overrepresented among patients with worse response to therapy in comparison to other genotypes (P < 0.001). On the contrary, patients carrying the A allele displayed lower grade of the disease at diagnosis more frequently than patients homozygous for the G allele (P = 0.037). Moreover, the AA homozygosity correlated with lower CD74 expression on B cells (P = 0.007). In conclusion, data from this study indicate that the CXCL12 rs1801157 G > A polymorphism may affect CLL development, disease progression as well as response to treatment.

Efficacy and safety of lenalidomide treatment in multiple myeloma (MM) patients--Report of the Polish Myeloma Group.

UNLABELLED: The aim of the multi-centre retrospective study was to evaluate the efficacy and safety of lenalidomide (LEN) therapy in patients with resistant or relapsed multiple myeloma (MM) as well as in patients with stable disease (LEN used due to neurological complications). The primary endpoint of this study was an overall response rate (ORR). The secondary endpoints were as follows: time to progression (TTP), overall survival (OS) and the safety of drug use. Data were collected in 19 centres of the Polish Multiple Myeloma Study Group. The study group consisted of 306 subjects: 153 females and 153 males. In 115 patients (38.8%, group A), a resistant myeloma was diagnosed; in 135 (44.1%, group B) a relapse, and in 56 (18.3%, group C) a stable disease were stated. In 92.8% of patients, LEN+DEX combination was used; in remaining group, LEN monotherapy or a combination therapy LEN+bortezomib or LEN+bendamustine and other were used. In the entire study group, ORR was 75.5% (including 12.4% patients achieving complete remission [CR] or stringent CR [sCR]). Median time to progression (TTP) was 20 months. Median overall survival (OS) was 33.3 months. The regression model for "treatment response" was on the borderline of statistical significance (p=0.07), however the number of LEN treatment cycles ≥ 6 (R(2)=17.2%), baseline LDH level (R(2)=1.1%) and no ASCT use (R(2)=1.7%) where the factors most affecting treatment response achievement. The regression model for dependant variable--"overall survival"--was statistically significant (p=0.0000004). Factors with the most impact on OS were as follows: number of LEN cycles treatment ≥ 6 (R(2)=16.7%), treatment response achievement (R(2)=6.9%), ß-2-microglobulin (ß-2-M) level (R(2)=4.8%), renal function (R(2)=3.0%) and lack of 3/4 grade adverse events (R(2)=1.4%). SUMMARY: LEN is an effective and safe therapeutic option, even in intensively treated resistant and relapsed MM patients, as well as in patients with stable disease and previous treatment-induced neurological complications. In particular, the number of LEN treatment cycles ≥ 6 was the factor which affected treatment response achievement the most, together with an important impact on OS.

Expression of bone morphogenetic proteins (BMPs) receptors in patients with B-cell chronic lymphocytic leukemia (B-CLL).

Bone morphogenetic proteins (BMPs) are multifunctional cytokines which belong to transforming growth factor ß (TGF ß) superfamily. They regulate proliferation, differentiation, and apoptosis in a variety of cells including hematopoietic cells. BMPs act because of binding to two types of serine/threonine kinase receptors: BMP type I receptors (IA and IB) and BMP type II receptor. Deregulation of BMPs signaling pathways has been reported in some of human cancers, but the role of BMPs in hematopoietic malignancies remains unknown. The aim of our study was to examine the percentage of expression of BMPs receptors on lymphocytes of patients with B-cell chronic lymphocytic leukemia (B-CLL). A total of 46 patients with B-CLL (27 men and 19 women) and 10 healthy persons were evaluated. Freshly isolated mononuclear cells were incubated with antibodies against BMPs receptors: BMPRIA, BMPRIB, and BMPRII and examined in 2-color flow cytometry. On cells of patients with B-CLL, the percentage of expression of BMP RIA, BMP RIB, and BMP RII was significantly higher than in normal cells of the control group. The percentage of the expression of BMP RIA and BMP RIB was higher in patients with advanced stage of disease.

Increased monocyte chemoattractant protein 1 (MCP-1/CCL-2) serum level in acute myeloid leukemia.

Acute myeloid leukaemia (AML) is an aggressive malignancy with accumulation of blasts in bone marrow. Myeloblasts can entry into peripheral blood stream and secondary localize in extramedullary sites. The regulation of this process has not been clearly explained so far, but interactions between some chemokines and their specific receptors could be one of the mechanisms responsible for such kind of migration. Monocyte chemoattractant protein 1 (MCP-1/CCL2) is the chemokine which could be involved in this process. The aim of the study was to evaluate plasma level of CCL2 in patients with AML. Plasma samples from 65 adult patients with AML taken before chemotherapy and in complete remission were measured by enzyme linked immunoassay to evaluate CCL2 levels. Control group consisted of 15 healthy subjects. In AML patients mean baseline CCL2 level (+/- SEM standard error of measurement) was significantly higher than in normal control: 365,26 +/- 5,62 pg/ml vs 265,56 +/- 5,48 pg/ml respectively (p<0.01). We demonstrate increased mean CCL2 plasma level in untreated patients with AML. Significantly lower plasma level of CCL2 was observed in patients with M4 and M5 AML subtypes according to FAB classification. In AML group chemotherapy did not reduce CCL2 plasma level.