Recombinant human CD19‐ligand protein as a potent anti‐leukaemic agent

Lack of CD24 Antigen Expression in B-Lineage Acute Lymphoblastic Leukemia Is Associated With Intrinsic Radiation Resistance of Primary Clonogenic Blasts

The authors conducted a flow cytometry immunophenotyping study in patients with acute lymphoblastic leukemia (ALL) from Natal, Rio Grande do Norte, Brazil. The patients (n = 126) were newly diagnosed using a panel of monoclonal antibodies: CD1a, CD2, CD3, CD4, CD7, CD8, CD10, CD13, CD33, CD14, CD19, CD22, CD79a, CD117, CD34, anti-IgM, anti-TdT, anti-HLA-Dr, and anti-human kappa and lambda light chains. Additional data, such as patients' age and gender, clinical and laboratory findings such as presence of tumor masses, lymphadenopathy, hepatomegaly, splenomegaly, leukemic infiltration in the central nervous system (CNS) were also investigated. Results showed that 56.7% of the cases were B-lineage ALL and 55% were T-cell ALL. Also, we found that males were more affected by the disease, regardless of immunological classification. The correlation between age and immunological subtypes showed that the B-lineage ALL occurred more frequently in patients aged under 15 while the T-cell ALL subtype was more frequent in adults. Immunophenotypic profiles and morphological subtypes showed a direct correlation between L3 subtype and B-lineage ALL, while L1 and L2 subtypes correlated more often with B-cell lineage and T-cell ALL, respectively. Correlation analysis between immunophenotypic and clinical profiles showed that T-cell ALL was more associated with a higher incidence of lymphadenopathy, hepatomegaly, splenomegaly and CNS leukemic infiltration, also showing a greater blast cell count in peripheral blood than the other subgroups. The presented data suggest that immunophenotyping is an important method in the diagnosis, monitoring and prognostic assessment in determining the pathological mechanisms of evolution of ALL.

Flow Cytometry Immunophemotyping Evaluation in the Diagnosis of Acute Lymphoblastic Leukemia in Patients from Rio Grande Do Norte State, Brazil

<div>Abstract<p>BH3 mimetic drugs may be useful to treat acute lymphoblastic leukemia (ALL) but the sensitivity of primary tumor cells has not been fully evaluated. Here, B-lineage ALL cell cultures derived from a set of primary tumors were studied with respect to sensitivity to the BH3 mimetics ABT-263 and ABT-199 and to Bcl-2 dependence and function. These ALL cells each expressed high levels of Bcl-2 and exhibited great sensitivity to ABT-263 and ABT-199, which induced rapid apoptotic cell death. BH3 profiling indicated that the ALL cultures were Bcl-2 dependent. Coimmunoprecipitation studies revealed a multifaceted role for Bcl-2 in binding proapoptotic partners including Bax, Bak, Bik, and Bim. ABT-263 disrupted Bcl-2:Bim interaction in cells. Mcl-1 overexpression rendered ALL cells resistant to ABT-263 and ABT-199, with Mcl-1 assuming the role of Bcl-2 in binding Bim. Freshly isolated pediatric ALL blasts also expressed high levels of Bcl-2 and exhibited high sensitivity to Bcl-2 inhibition by the BH3 mimetic compounds. Overall, our results showed that primary ALL cultures were both more sensitive to BH3 mimetics and more uniform in their response than established ALL cell lines that have been evaluated previously. Furthermore, the primary cell model characterized here offers a powerful system for preclinical testing of novel drugs and drug combinations to treat ALL. <i>Cancer Res; 75(7); 1366–75. ©2015 AACR</i>.</p></div>

Children with relapsed acute lymphoblastic leukemia (ALL) in low-income and middle-income countries rarely survive. The Pediatric Hematology-Oncology Association of Central America (AHOPCA) developed the AHOPCA-ALL REC 2014 protocol to improve outcomes in resource-constrained settings without access to stem cell transplantation. The AHOPCA-ALL REC 2014 protocol was based on a modified frontline induction phase 1A, a consolidation therapy with six modified R-blocks derived from the ALL-Berlin-Frankfurt-Munster REZ 2002 protocol and intermittent maintenance therapy. Children with B-lineage ALL were eligible after a late medullary relapse, an early or late combined relapse, or any extramedullary relapses. Those with T-lineage ALL were eligible after early and late extramedullary relapses, as were those with both B-lineage and T-lineage relapses occurring at least 3months after therapy abandonment. The study population included 190 patients with T-lineage (n=3) and B-lineage (n=187) ALL. Of those with B-lineage ALL, 25 patients had a very early extramedullary relapse, 40 had an early relapse (32 extramedullary and 8 combined), and 125 had a late relapse (34 extramedullary, 19 combined, and 72 medullary). The main cause of treatment failure was second relapse (52.1%). The 3-year event-free survival rate (± standard error) was 25.9%±3.5%, and the 3-year overall survival rate was 36.7%±3.8%. The 3-year event-free survival rate was 47.2%±4.7% for late relapses. The most frequently reported toxicity was grade 3 or 4 infection. Mortality during treatment occurred in 17 patients (8.9%), in most cases because of infectious complications. Selected children with relapsed ALL in Central America can be cured with second-line regimens even without access to consolidation with stem cell transplantation. Children in low-income and middle-income countries who have lower risk relapses of ALL should be treated with curative intent.

Zebrafish ALL Driven By HumanMYCand a New Technique to Biopsy Living Fish

Para-NO-aspirin inhibits NF-κB and induces apoptosis in B-cell progenitor acute lymphoblastic leukemia

In Vitro and In Vivo Activity of Topotecan Against Human B-Lineage Acute Lymphoblastic Leukemia Cells

Targeting Pre-B Cell Receptor and BCL6 In TCF3-PBX1 B-Lineage Acute Lymphoblastic Leukemia

Characteristics and Outcome of Adolescents with Acute Lymphoblastic Leukemia (ALL) Differ from Young Children in the B-Cell Lineage but Not in the T-Cell Lineage: Experience of the ALL Israeli National Studies (INS).

Rapid Identification of BCR/ABL1 -like Acute Lymphoblastic Leukemia (ALL) Cases By Quantitative Real Time-PCR (Q-RT-PCR). Generation and Validation of a Predictive Statistical Model

Cyclosporin A Induces Apoptosis in Childhood Acute Lymphoblastic Leukemia Cells

BackgroundNeuropilins are transmembrane glycoproteins that act as receptors for vascular endothelial growth factors and are involved in the process of tumor angiogenesis.ObjectiveThe aim of this work was to study the prognostic value of Neuropilin-1 (NRP-1) expression in Egyptian children with B-lineage acute lymphoblastic leukemia (ALL).Patients and methodsThis study was conducted on fifty children with newly diagnosed B-lineage ALL, admitted to Oncology Unit, Pediatric Department, Tanta University Hospitals in the period from August 2010 to March 2014. This series included 32 males and 18 females with ages ranging from 3–17 years and a mean value of 9 ± 3.5 years. Twenty healthy children, age and sex matched, were also included in this study as a control group. For all patients, the following examens were done: Bone marrow aspiration, cytochemistry, immunophenotyping and estimation of Neuropilin-1 expression on blast cells by flow cytometry.ResultsThe present study revealed highly significant differences in Neuropilin-1 expression between B-lineage ALL lymphoblasts and control lymphocytes. A significant higher Neuropilin-1 expression was found in pre-B ALL (74.04%) compared with early pre-B (23.55%). Neuropilin-1 positive expression was associated with significantly higher white blood cells count (Mean = 69.3±18.53 ×103/mm3 versus 32.5±11.64 ×103/mm3 and p=0.003), bone marrow blasts percentage (Mean=76.12±21.4 % versus 41.2±19.71% and p= 0.003), serum lactate dehydrogenase levels (Mean=1992.2 ± 58.6 unit/L versus 955.1± 234.7 unit/L and p=0.001) at diagnosis compared with negative Neuropilin-1 expression. The levels of Neuropilin-1 on BM blasts at diagnosis were higher in patients who subsequently relapsed (Mean=53.8 ± 27.1) or later died (Mean=81.51 ± 9.94) during the period of follow-up compared to those who achieved and maintained complete remission (Mean=18.17 ± 10.4) with p value of 0.001. Furthermore, patients with higher Neuropilin-1 expression had significantly shorter overall survival (Median 27.99 months and p= 0.0133) and disease-free survival (Median=10.23 months and p= 0.0002) than patients with low Neuropilin-1 expression (Median disease-free survival was 38.7 months).ConclusionOur findings suggest that Neuropilin-1 is a poor prognosis factor in children with B-lineage ALL and so we recommend the inclusion of Neuropilin-1 as a prognostic marker in children with B-lineage ALL. Its presence at high levels suggests a poor prognosis, and the necessity of intensive therapeutic intervention.

Adult acute lymphoblastic leukaemia

Differences in constitutive and post-methotrexate folylpolyglutamate synthetase activity in B-lineage and T-lineage leukemia