Childhood near-tetraploid acute lymphoblastic leukemia: an EGIL study on 36 cases.

Objectives: Patients with near-tetraploid (karyotype: 81 - 103 chromosomes) acute lymphoblastic leukemia (NT-ALL) constitute about 1% of childhood ALL and data reported on them are limited and controversial. The aim of the study was to enlarge the knowledge on these rarely occurring ALL.

Methods: The members of the European Group for Immunophenotyping of Leukemias (EGIL) searched retrospectively their databases for NT-ALL patients.

Neoplastic circulating endothelial-like cells in patients with acute myeloid leukaemia.

Accumulating evidence suggests that angiogenesis may play a key role in the pathogenesis of leukaemic disorders. Several studies have shown that bone marrow-derived endothelial cells (EC) may contribute to tumour angiogenesis and that in the peripheral blood of cancer patients there is an increased amount of circulating ECs (CECs) that may participate to new vessel formation. In this report, we showed that, in seven acute myeloid leukaemia (AML) patients with known cytogenetic abnormalities, CEC levels were significantly increased in comparison with controls and that a significant proportion of these CECs carried the same chromosomal aberration as blast cells (20-78%, mean value 42.

Mobilization of endothelial progenitor cells in patients with hematological malignancies after treatment with filgrastim and chemotherapy for autologous transplantation.

In recent years, endothelial progenitor cells (EPCs), gave rise to increasing interest because of their possible use as a therapeutic tool in the treatment of vascular lesions in ischemic tissues or as a target for anti neoplastic therapy. It has been shown that several drugs can increase the number of EPCs into the peripheral blood (PB). However, there is insufficient data concerning the mobilization and collection of EPCs during CD34+ cell mobilization.

The biological characteristics of CD34+ CD2+ adult acute promyelocytic leukemia and the CD34 CD2 hypergranular (M3) and microgranular (M3v) phenotypes.

Background And Objectives: Acute promyelocytic leukemia (APL) is characterized by leukemic cells blocked at the promyelocytic stage of granulocytic differentiation. To date, it is still not clear whether CD34 expression identifies a subset of APL patients with peculiar characteristics. We, therefore, conducted a detailed analysis of CD34 expression at diagnosis in 136 adults with de novo APL.

Validation of an interphase fluorescence in situ hybridization approach for the detection of MLL gene rearrangements and of the MLL/AF9 fusion in acute myeloid leukemia.

To validate a 2-step FISH assay for the identification of the t(9;11)(p22;q23), 96 acute myeloid leukemias were studied by cytogenetic analysis, FISH and molecular biology. After a first FISH step using an MLL probe, 24/27 cases with 11q23 break showed MLL rearrangement. Southern blotting confirmed FISH data.

Neoplastic circulating endothelial cells in multiple myeloma with 13q14 deletion.

In multiple myeloma (MM), circulating endothelial cells (CECs) represent a vascular marker of angiogenesis and may reflect tumor mass. In this report, we showed that, in 5 MM patients with 13q14 deletion, CECs carried the same chromosome aberration as the neoplastic plasma cells (11%-32% of CECs with 13q14 deletion). Most of the CECs displayed immunophenotypic features of endothelial progenitor cells as they expressed CD133, a marker gradually lost during endothelial differentiation and absent on mature endothelial cells.

A case of advanced Hodgkin lymphoma with breast involvement treated with a combination of gemcitabine and pegylated liposomal doxorubicin.

Gemcitabine in combination with pegylated liposomal doxorubicin has been recognized as an effective treatment in patients with refractory solid tumors. To our knowledge, this is the first case of relapsed Hodgkin lymphoma with breast involvement successfully treated with this association.

The role of rHuEpo in low-risk myelodysplastic syndrome patients.

Myelodysplastic syndromes (MDS) are clonal disorders of the haemopoietic stem cell characterized by peripheral cytopenias that are the result of abnormal haemopoietic differentiation and maturation. Approximately 90% of MDS patients present with anemia at the beginning or during the course of the disease and often require transfusions. The rationale for treating anemic MDS patients with recombinant human erythropoietin (rHuEpo), alone or in combination with other growth factors, is based on the possibility of overcoming the defective proliferation and maturation of erythroid precursors through the inhibition of bone marrow apoptosis, the enhancement of the differentiation of preleukemic progenitor cells or the stimulation of the growth of residual normal haematopoietic cells.

Dendritic cells and vascular endothelial growth factor in colorectal cancer: correlations with clinicobiological findings.

Objective: Dendritic cells (DC) are central to the development of immune system responses. In a cohort of 54 patients affected by colorectal cancer, we prospectively investigated the number of peripheral blood (PB) DC type 1 (DC1) and type 2 (DC2) and correlated their counts and functionality to the stage of the disease and to vascular endothelial growth factor (VEGF) levels.

Results: At diagnosis, compared with healthy controls, patients presented reduced PBDC1 and PBDC2 numbers (p < 0.

A His-155 to Tyr polymorphism confers gain-of-function to the human P2X7 receptor of human leukemic lymphocytes.

The P2X(7)R is an ATP-gated cation channel expressed in hemopoietic cells that participates in both cell proliferation and apoptosis. Expression and function of the P2X(7)R have been associated with the clinical course of patients affected by chronic lymphocytic leukemia (CLL). Functional variants causing loss-of-function of the P2X(7)R have been identified, namely, polymorphisms 1513A>C (E496A), 1729T>A (I568N), and 946G>A (R307Q).

Use of granulocyte-colony stimulating factor during acute myocardial infarction to enhance bone marrow stem cell mobilization in humans: clinical and angiographic safety profile.

Aims: There is increasing evidence that stem cell (SC) mobilization to the heart and their differentiation into cardiac cells is a naturally occurring process. We sought to assess the safety and feasibility of granulocyte-colony stimulating factor (G-CSF) administration in humans to enhance SC mobilization and left ventricle (LV) injury repair during myocardial infarction (MI).

Methods And Results: Twenty patients with STEMI (mean age, 61+/-10 years), of whom 14 were submitted to primary percutaneous coronary intervention, were randomized to G-CSF (5 microg/kg/day s.

A comprehensive genetic classification of adult acute lymphoblastic leukemia (ALL): analysis of the GIMEMA 0496 protocol.

The Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) 0496 protocol, through the central handling of bone marrow samples at presentation, allowed us to combine cytogenetic and molecular information on a large series of adults with acute lymphoblastic leukemia (ALL) treated homogeneously, enabling us to define as broadly as possible their genetic profile and to determine the impact on outcome of the cytogenetic-molecular signature. Of 414 patients centrally processed, 325 were considered for the categorization into the following cytogenetic-molecular subgroups: normal, t(9;22)/BCR-ABL, t(4;11)/MLL-AF4, t(1;19)/E2A-PBX1, 9p/p15-p16 deletions, 6q deletions, miscellaneous structural abnormalities, and hyperdiploid. The inclusion into each subgroup was based on a hierarchical approach: molecular abnormalities with adverse prognosis had precedence over karyotypic changes with less-defined prognosis and the latter over ploidy.

Flow cytometric detection of accelerated telomere shortening in myelodysplastic syndromes: correlations with aetiological and clinical-biological findings.

Using quantitative fluorescence in situ hybridisation and flow cytometry (flow-FISH), we investigated the biological and clinical relevance of telomere length in 55 patients affected by myelodysplastic syndromes (MDS) compared with 55 sex- and age-matched controls. We found that telomere fluorescence in MDS granulocytes, and CD34+ cells did not decline with age as in normal controls and that MDS granulocytes and CD34+ cells had significantly shorter telomeres than healthy controls. A significant higher incidence of cases with intermediate-unfavourable cytogenetics and International Prognostic Scoring System (IPSS) int-2/high-risk group was observed among patients with lower telomere fluorescence.

Abnormalities of chromosomes 1p34-36, 4p16, 4q35, 9q11-32 and +7 represent novel recurrent cytogenetic rearrangements in chronic lymphocytic leukemia.

Karyotypes were studied in over 250 cases of CLL seen at our Institution and 12 cases with a previously undescribed chromosome abnormality were identified. Cytogenetic and clinicobiological features in these patients are described. Fluorescence in situ hybridization using probes for the detection of +12 and deletions of 13q14, 17p13, and 11q22-23 was performed.

In patients with myelodysplastic syndromes response to rHuEPO and G-CSF treatment is related to an increase of cytogenetically normal CD34 cells.

The in vivo effect of recombinant human erythropoietin (rHuEpo) and granulocyte colony-stimulating factor (G-CSF) combined treatment on CD34(+) cells was evaluated by fluorescence in situ hybridization (FISH) in 13 myelodysplastic syndrome (MDS) patients with known cytogenetic abnormalities. After treatment, responsive patients presented a significantly lower proportion of FISH abnormal CD34(+) cells than before treatment (P = 0.003), and in comparison with unresponsive cases (P = 0.

CD34+ and endothelial progenitor cells in patients with various degrees of congestive heart failure.

Background: Peripheral blood CD34(+) cells and circulating endothelial progenitor cells (EPCs) increase in myocardial infarction and vascular injuries as a reflection of endothelial damage. Despite the occurrence of endothelial dysfunction in heart failure (HF), no data are available on EPC mobilization in this setting. We investigated the pattern of CD34(+) cells and EPC mobilization during HF and their correlation with the severity and origin of the disease.

Dendritic cell recovery after allogeneic stem-cell transplantation in acute leukemia: correlations with clinical and transplant characteristics.

We have analyzed the kinetics of reconstitution of circulating dendritic cell (DC) subsets (myeloid-DC1 and lymphoid-DC2) in 19 patients affected by acute leukemia undergoing allogeneic hematopoietic stem-cell transplantation (HSCT). We have found that pretransplant DC1 and DC2 were lower in leukemic patients than in healthy subjects (P = 0.003 and P = 0.

"In vitro" evaluation of bone marrow angiogenesis in myelodysplastic syndromes: a morphological and functional approach.

In myelodysplastic syndromes (MDS), ineffective hematopoiesis and cytopenia may arise either from increased susceptibility to apoptosis of hematopoietic cells, or possibly from alterations of bone marrow stroma that contributes to defective development of marrow lineages. In order to test the significance of the endothelial growth in MDS patients, two in vitro assays are presented in this study: a long-term culture method for the detection of human bone marrow endothelial colonies (CFU-En) (77 patients) and a human primary model for the evaluation of the influence of a "bone marrow conditioned medium" on the formation of new vessels in a culture matrix ("angio-kit assay") (in 24 out 77 patients). The in vitro growth pattern of bone marrow CFU-En as well as the generation of microvessels in the angio-kit system was increased in RA, RARS and RAEB in comparison with controls.

CXCR-4 expression on bone marrow CD34+ cells prior to mobilization can predict mobilization adequacy in patients with hematologic malignancies.

To investigate the mechanisms of mobilization and of the factors implicated in the homing of progenitors and possibly understand the reasons for unpredicted mobilization failure, we analyzed CXCR-4 (CD184) expression on bone marrow (BM) CD34+ cells prior to peripheral blood stem cell (PBSC) mobilization in 24 patients affected by hematologic malignancies (non-Hodgkin lymphoma, multiple myeloma, and acute myeloid leukemia). We wanted to determine whether the level of CXCR-4 expressed by hematopoietic stem cells could influence mobilization process and therefore could be considered a predictive factor for mobilization adequacy. These data were also compared with stromal cell function as assessed by colony forming unit-fibroblast (CFU-F) and CFU endothelial cells (CFU-En) assays and stromal layer confluence capacity exhibited by patients' BM cells.

Differentiation of follicular dendritic sarcoma cells into functional myeloid-dendritic cell-like elements.

In a rare case of follicluar dendritic cell sarcoma, malignant cells were isolated and cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 4 (IL-4) and tumor necrosis factor alpha (TNF-alpha). After 14 d, 15% of neoplastic cells differentiated into myeloid-dendritic cell-like elements as demonstrated by immunological and functional characteristics. These cells showed the same cytogenetic abnormality of the malignant clone (fluorescence in situ hybridisation analysis performed on CD1a+ cells) and were able to induce allogenic T-cell proliferation in the mixed leucocyte reaction.

Chronic lymphocytic leukemia patients with highly stable and indolent disease show distinctive phenotypic and genotypic features.

Different biologic features have been associated with a more or less aggressive clinical course in chronic lymphocytic leukemia (CLL). In the present study, 20 patients with highly stable CLL observed at a single institution over a period of 10 to 23 years and who never required treatment were extensively characterized. The aim was to identify a distinct and reproducible biologic profile associated with disease stability that may be used to recognize at presentation CLL patients who are likely to have a very benign clinical course and for whom treatment is not indicated.

Soluble urokinase-type plasminogen activator receptor (suPAR) as an independent factor predicting worse prognosis and extra-bone marrow involvement in multiple myeloma patients.

The urokinase-type plasminogen activator (uPA) system, which consists of a proteinase (uPA), a receptor (uPAR or CD87) and inhibitors, is involved in proteolysis, cell migration, tissue remodelling, angiogenesis and cell adhesion. Recent findings suggest that malignant plasma cells express uPA and uPAR. The expression of these factors could represent a process by which myeloma plasma cells interact with the bone marrow (BM) environment and influence important biological events such as bone matrix degradation, plasma cell invasion and homing and, possibly, clinical evolution.

rHuEpo administration in patients with low-risk myelodysplastic syndromes: evaluation of erythroid precursors' response by fluorescence in situ hybridization on May-Grunwald-Giemsa-stained bone marrow samples.

The issue of whether, in patients affected by myelodysplastic syndromes (MDS), haematological response to cytokines, particularly to recombinant human erythropoietin (rHuEpo), is a phenomenon related to the stimulation of normal haemopoietic cells or to the differentiation of cells belonging to the abnormal clone remains an open question. To assess the pattern of response to rHuEpo treatment of bone marrow (BM) cells, we evaluated in 13 low-risk MDS patients with known cytogenetic abnormalities the number of cytogenetically normal and abnormal cells by conventional cytogenetic analysis (CCA) and by a fluorescence in situ hybridization (FISH) technique, enabling the simultaneous visualization of FISH chromosomal abnormalities in morphologically and immunophenotypically identifiable BM elements. Patients responding to rHuEpo presented a lower number of abnormal metaphases at diagnosis in comparison with patients who did not respond (22.

Late appearance of the 11q22.3-23.1 deletion involving the ATM locus in B-cell chronic lymphocytic leukemia and related disorders. Clinico-biological significance.

Background And Objectives: Chromosome 11q22.3-23.1 deletions involving the ataxia-teleangiectasia mutated (ATM) locus (11q-/ATM+/-) are detected at diagnosis in 10-20% of cases of B-cell chronic lymphocytic leukemia (CLL) and are associated with a relatively aggressive disease.