High CD74 expression correlates with ZAP70 expression in B cell chronic lymphocytic leukemia patients.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in Western countries. It is characterized by heterogeneous clinical course of the disease and new prognostic factors are still needed. CD74 plays an important role in signal transduction in B cell proliferation and survival pathway.

Polymorphisms of TNF and IL-10 genes and clinical outcome of patients with chronic lymphocytic leukemia.

Genetic variations in tumor necrosis factor (TNF) and interleukin-10 (IL-10) were reported to influence susceptibility to and outcome of patients with non-Hodgkin lymphoma. Therefore, we investigated whether single nucleotide polymorphisms in TNF and IL-10 may play a role in the clinical course of patients with chronic lymphocytic leukemia (CLL). TNF-308G>A, IL-10-3575T>A, and IL-10-1082A>G seem to be functionally relevant, were genotyped in 292 previously untreated patients with CLL.

High expression of hematopoietic cell specific Lyn substrate-1 (HS1) predicts poor survival of B-cell chronic lymphocytic leukemia patients.

Unlabelled: B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in adults in western countries. HS1 protein regulates leukemic cell migration and homing, and can indirectly promote disease progression and influence patient survival. The aim of this study was to evaluate HS1 expression in CLL patients in connection with other known prognostic factors and patients' survival.

Hematopoietic stem cell transplantation for T315I-mutated chronic myelogenous leukemia.

Background: The T315I mutation of BCR/ABL gene is known to produce complete resistance of chronic myelogenous leukemia (CML) to all currently available BCR/ABL inhibitors. The data suggesting poor median survival of these patients may indicate that they should be primary candidates for allogeneic stem cell transplantation (alloSCT). However, evidence on efficiency of this treatment modality in CML with T315I mutation is lacking.

A diagnostically difficult case of chronic myeloid neoplasm with eosinophilia and abnormalities of PDGFRA effectively treated with imatinib in accelerated phase: case report.

Chronic myeloid neoplasm with eosinophilia and abnormalities of platelet-derived growth factor receptor alpha (PDGFRA), referred to until 2008 as chronic eosinophilic leukemia, is distinguished from hypereosinophilic syndrome (HES), if accompanied by genetic abnormalities that enable to determine eosinophil clonality. Typically, HES has a benign course and glucocorticosteroids suffice to achieve remission. In chronic myeloid neoplasm with eosinophilia and abnormalities of PDGFRA the FIP1L1-PDGFRA fusion gene can be detected.

Frequency of BCR-ABL gene mutations in Polish patients with chronic myeloid leukemia treated with imatinib: a final report of the MAPTEST study.

Introduction: The presence of BCR-ABL oncogene mutations in patients with chronic myeloid leukemia (CML) may be responsible for the failure of tyrosine kinase inhibitor treatment.

Objectives: The aim of the study was to evaluate the frequency of BCR-ABL gene mutations in patients with CML (the MAPTEST study) treated with imatinib (IM).

Patients And Methods: Direct sequencing analysis of BCR-ABL gene was performed in 92 patients treated with IM for more than 3 months.

T-cell abnormalities are present at high frequencies in patients with hypereosinophilic syndrome.

Background: A T-cell clone, thought to be the source of eosinophilopoietic cytokines, identified by clonal rearrangement of the T-cell receptor and by the presence of aberrant T-cell immunophenotype in peripheral blood defines lymphocytic variant of hypereosinophilic syndrome (L-HES).

Design And Methods: Peripheral blood samples from 42 patients who satisfied the diagnostic criteria for HES were studied for T-cell receptor clonal rearrangement by polymerase chain reaction according to BIOMED-2. The T-cell immunophenotype population was assessed in peripheral blood by flow cytometry.

A single weekly dose of imatinib is sufficient to induce and maintain remission of chronic eosinophilic leukaemia in FIP1L1-PDGFRA-expressing patients.

Hypereosinophilic syndrome (HES) is defined as chronic, unexplained hypereosinophilia with organ involvement. A subset of HES patients presents an interstitial deletion in chromosome 4q12, which leads to the expression of an imatinib-responsive fusion gene, FIP1L1-PDGFRA. These patients are diagnosed as chronic eosinophilic leukaemia (CEL).

Predictive value of RT-PCR PML-RARA transcript monitoring for extramedullary relapse of acute promyelocytic leukemia in the pleura, heart and pericardium after allogeneic SCT.

Background: We report a patient with acute promyelocytic leukemia (APL) relapse in extremely rare sites--the pleura, heart and pericardium without evidence of bone marrow infiltration and with molecular evidence of disease after allogeneic stem cell transplantation (alloSCT).

Case Description: Presented patient underwent alloSCT in second complete hematological and cytogenetic remission with presence of promyelocytic leukemia-retinoic acid receptor A (PML-RARA) detected in reverse transcription-polymerase chain reaction (RT-PCR) with sensitivity of 10(-2). After transplant, this patient remained in complete hematological and cytogenetic remission but nested RT-PCR assays with detection thresholds of 10(-3)/10(-4) were positive for PML-RARA rearranged gene even chimerism tests showed 100% of donor profile.

Complete cytogenetic and molecular response after imatinib treatment for chronic myeloid leukemia in a patient with atypical karyotype and BCR-ABL b2a3 transcript.

The molecular hallmark of CML is the BCR-ABL fusion gene, usually with specific breakpoints within ABL intron 1 and BCR introns b2, b3, and e19. The amplification of the BCR-ABL hybrid gene resulting from additional copies of the Ph chromosome has been identified as a mechanism for imatinib (IM) resistance. Cytogenetic clonal evolution correlates with the accelerated phase of leukemia, whereas deletions in the derivative chromosome 9 are associated with a poor prognosis.

Transformation in lymphomas--morphological, immunophenotypic and molecular features.

During the course of lymphoma, a clinically more aggressive process with different morphology may develop, referred to as lymphoma transformation. Clonal relationship and pathogenic mechanism of this process are widely debated. The aim of the study was to evaluate morphology, immunophenotype (including EBV status) and clonal relationship in nine cases of lymphoma transformation.

Expression and oncogenic role of Brk (PTK6/Sik) protein tyrosine kinase in lymphocytes.

Tyrosine kinases play a fundamental role in cell proliferation, survival, adhesion, and motility and have also been shown to mediate malignant cell transformation. Here we describe constitutive expression of the protein tyrosine kinase Brk in a large proportion of cutaneous T-cell lymphomas and other transformed T- and B-cell populations. The kinase is expressed in the nuclear localization and activated state.

Immunosuppressive TOR kinase inhibitor everolimus (RAD) suppresses growth of cells derived from posttransplant lymphoproliferative disorder at allograft-protecting doses.

Background: Posttransplant lymphoproliferative disorders (PTLDs) represent a life-threatening complication of standard immunosuppressive therapy. The impact of novel, rapamycin-related immunosuppressive drugs on the pathogenesis of PTLDs remains undefined.

Methods: We tested the effect of everolimus (RAD, Novartis Pharma AG, Basel, Switzerland) on human PTLD-derived cells using in vitro assays and an in vivo severe combined immunodeficiency disease mouse xenotransplant model.

Expression of SHP-1 phosphatase indicates post-germinal center cell derivation of B-cell posttransplant lymphoproliferative disorders.

SHP-1 tyrosine phosphatase acts as a negative regulator of signaling by receptors for growth factors, cytokines, and chemokines and by receptors involved in immune response. Our recent study showed that SHP-1 is tightly regulated at various stages of B-cell differentiation and is expressed in the mantle and marginal zones, interfollicular B cells, and plasma cells, whereas it is nondetectable in germinal center cells. In this study we evaluated expression of SHP-1 in vitro and in vivo in nine cell lines representing three different types of EBV+ B-cell populations closely resembling or derived from posttransplant lymphoproliferative disorders (PTLDs).

Multilevel dysregulation of STAT3 activation in anaplastic lymphoma kinase-positive T/null-cell lymphoma.

Accumulating evidence indicates that expression of anaplastic lymphoma kinase (ALK), typically due to t(2;5) translocation, defines a distinct type of T/null-cell lymphoma (TCL). The resulting nucleophosmin (NPM) /ALK chimeric kinase is constitutively active and oncogenic. Downstream effector molecules triggered by NPM/ALK remain, however, largely unidentified.