(acute lymphocytic leukemia)
- MicroRNA-155 in serum-derived extracellular vesicles as a potential biomarker for hematologic malignancies - a short report. [Journal Article]
- COCell Oncol (Dordr) 2016 Oct 19
- CONCLUSIONS: Our data indicate that EV miR155 may serve as an attractive new, non-invasive diagnostic biomarker in human hematologic malignancies.
- Treating adults with acute lymphocytic leukemia: new pharmacotherapy options. [Journal Article]
- EOExpert Opin Pharmacother 2016 Oct 19
- Advances in acute lymphocytic leukemia (ALL) therapy has led to long-term survival rates in children. However, only 30%-40% of adults achieve long-term disease-free survival. After relapse, the outco...
Advances in acute lymphocytic leukemia (ALL) therapy has led to long-term survival rates in children. However, only 30%-40% of adults achieve long-term disease-free survival. After relapse, the outcome of salvage chemotherapy is very disappointing with less than 10% of long survival. Novel agents are therefore desperately required to improve response rates and survival, but also the quality of life of patients. Areas covered. The following review is a comprehensive summary of various novel options reported over the past few years in the therapeutic area of adult ALL. Expert opinion. Identifying key components involved in disease pathogenesis may lead to new approaches. In a near future, the incorporation of monoclonal antibodies and T-cell directed approaches including blinatumomab and chimeric antigen receptor T cells may increase the cure rates and may reduce the need for intensive therapy.
- E2A-PBX1 remodels oncogenic signaling networks in B-cell precursor acute lymphoid leukemia. [Journal Article]
- CRCancer Res 2016 Oct 7
- There is limited understanding of how signaling pathways are altered by oncogenic fusion transcription factors that drive leukemogenesis. To address this, we interrogated activated signaling pathways...
There is limited understanding of how signaling pathways are altered by oncogenic fusion transcription factors that drive leukemogenesis. To address this, we interrogated activated signaling pathways in a comparative analysis of mouse and human leukemias expressing the fusion protein E2A-PBX1, which is present in 5-7% of pediatric and 50% of pre-B-cell receptor (preBCR+) acute lymphocytic leukemia (ALL). In this study, we describe remodeling of signaling networks by E2A-PBX1 in pre-B-ALL which result in hyperactivation of the key oncogenic effector enzyme PLCγ2. Depletion of PLCγ2 reduced proliferation of mouse and human ALLs, including E2A-PBX1 leukemias, and increased disease-free survival after secondary transplantation. Mechanistically, E2A-PBX1 bound promoter regulatory regions and activated the transcription of its key target genes ZAP70, SYK, and LCK, which encode kinases upstream of PLCγ2. Depletion of the respective upstream kinases decreased cell proliferation and phosphorylated levels of PLCγ2 (pPLCγ2). Pairwise silencing of ZAP70, SYK or LCK showed additive effects on cell growth inhibition, providing a rationale for combination therapy with inhibitors of these kinases. Accordingly, inhibitors such as the SRC family kinase (SFK) inhibitor dasatinib reduced pPLCγ2 and inhibited proliferation of human and mouse preBCR+/E2A-PBX1+ leukemias in vitro and in vivo. Further, combining small-molecule inhibition of SYK, LCK and SFK showed synergistic interactions and preclinical efficacy in the same setting. Our results show how the oncogenic fusion protein E2A-PBX1 perturbs signaling pathways upstream of PLCγ2 and renders leukemias amenable to targeted therapeutic inhibition.
- Biallelic loss of CDKN2A is associated with poor response to treatment in pediatric acute lymphoblastic leukemia. [Journal Article]
- LLLeuk Lymphoma 2016 Oct 18; :1-10
- The inactivation of tumor suppressor genes located within 9p21 locus (CDKN2A, CDKN2B) occurs in up to 30% of children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), but its independent...
The inactivation of tumor suppressor genes located within 9p21 locus (CDKN2A, CDKN2B) occurs in up to 30% of children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), but its independent prognostic significance remains controversial. In order to investigate the prognostic impact of deletions and promoter methylation within 9p21, 641 children with newly diagnosed BCP-ALL using methylation specific multiplex ligation-dependent probe amplification (MS-MLPA) were investigated. A total of 169 (26.4%) microdeletions in 9p21 were detected, of which 71 were homozygous. Patients with CDKN2A homozygous deletions were older at diagnosis (p < .001), more frequently steroid resistant (p = .049), had higher WBC count (p < .001), higher MRD at Day 15 (p = .013) and lower relapse-free survival [p = .028, hazard ratio: 2.28 (95% confidence interval: 1.09-4.76)] than patients without these alterations. CDKN2A homozygous deletions coexisted with IKZF1 and PAX5 deletions (p < .001). In conclusion, CDKN2A homozygous deletions, but not promoter methylation, are associated with poor response to treatment and increased relapse risk of pediatric BCP-ALL.
- Coexistence Of Chronic Lymphocytic Leukemia And Acute Myeloid Leukemia. [Journal Article]
- TJTurk J Haematol 2016 Oct 18
- A 76-years old man presented with leucocytosis (86x109/l), fever, pneumonia and significant weight loss. He had a history of chronic lymphocytic leukemia diagnosed five years earlier and he responded...
A 76-years old man presented with leucocytosis (86x109/l), fever, pneumonia and significant weight loss. He had a history of chronic lymphocytic leukemia diagnosed five years earlier and he responded with partial remission to the treatment with continuous low doses of chlorambucil. Analysis of blood smear, bone marrow aspiration and bone marrow biopsy revealed predomination of small lymphocytes, but 22% of cells were blasts negative to cytochemical stainings (Figure 1). Flow cytometric analysis showed two distinct populations: 65% of cells was small to moderate in size, CD19+, CD45+, CD5+, CD20+/-, but 30% of cells were large, CD34+, CD13+, HLA DR+, CD65+, CD45+, MPO weakly positive and CD33, CD14, CD15, CD16 negative. Immunophenotyping confirmed coexistence of chronic lymphocytic leukemia and poorly differentiated acute myeloid leukemia. Conventional cytogenetic testing did not show any chromosomal abnormalities. Patient was treated with intensive antibiotics and received one course of chemotherapy, but did not achieve remission and died two months later. Coexistence of chronic lymphocytic leukemia and acute myeloid leukemia is rare (1). Therapy-related acute myeloid leukemia can develop after treatment of chronic lymphocytic leukemia with alkylating agents, nucleoside analogs or with combination chemotherapy, but two leukemias can also originated independently (2,3).
- Two fatal herpesvirus cases: Treatable but easily missed diagnoses. [Journal Article]
- IIDCases 2016; 6:65-67
- Ill or immunosuppressed hospital patients are at increased risk for herpes simplex and herpes zoster virus infections, with high potential morbidity and mortality. Here, we present two cases of react...
Ill or immunosuppressed hospital patients are at increased risk for herpes simplex and herpes zoster virus infections, with high potential morbidity and mortality. Here, we present two cases of reactivation of herpes virus infections with delay in diagnosis, with ultimately fatal results. Since these infections are treatable, it is important to keep a high index of suspicion to facilitate early diagnosis and treatment.
- Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate. [Journal Article]
- NBioNat Biotechnol 2016 Oct 10
- Assays that can determine the response of tumor cells to cancer therapeutics could greatly aid the selection of drug regimens for individual patients. However, the utility of current functional assay...
Assays that can determine the response of tumor cells to cancer therapeutics could greatly aid the selection of drug regimens for individual patients. However, the utility of current functional assays is limited, and predictive genetic biomarkers are available for only a small fraction of cancer therapies. We found that the single-cell mass accumulation rate (MAR), profiled over many hours with a suspended microchannel resonator, accurately defined the drug sensitivity or resistance of glioblastoma and B-cell acute lymphocytic leukemia cells. MAR revealed heterogeneity in drug sensitivity not only between different tumors, but also within individual tumors and tumor-derived cell lines. MAR measurement predicted drug response using samples as small as 25 μl of peripheral blood while maintaining cell viability and compatibility with downstream characterization. MAR measurement is a promising approach for directly assaying single-cell therapeutic responses and for identifying cellular subpopulations with phenotypic resistance in heterogeneous tumors.
- The Promise of Chimeric Antigen Receptor T-Cell Therapy. [Review]
- OOncology (Williston Park) 2016 Oct 15; 30(10)
- Chimeric antigen receptors (CARs) are engineered molecules that can be introduced into T cells to enable them to target specific tumor antigens. CAR T cells targeting CD19 have shown promise in patie...
Chimeric antigen receptors (CARs) are engineered molecules that can be introduced into T cells to enable them to target specific tumor antigens. CAR T cells targeting CD19 have shown promise in patients with relapsed and refractory B-cell neoplasms, including those with acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphomas. Notably, durable responses have been observed in patients who had not undergone consolidative stem cell transplant, a finding that correlates with reports of T-cell persistence and B-cell aplasia in studies of anti-CD19 treatment in vivo. Cytokine release syndrome, correlating with activation and expansion of T cells, and neurologic toxicity are the most significant treatment-related adverse effects. Efforts are underway to extend the benefits of immunotherapy with anti-CD19 CAR T cells to other targets and tumor types.
- Efficacy of Compound Kushen Injection in Combination with Induction Chemotherapy for Treating Adult Patients Newly Diagnosed with Acute Leukemia. [Journal Article]
- EBEvid Based Complement Alternat Med 2016; 2016:3121402
- We assessed the clinical effectiveness and safety of CKI (compound Kushen injection) plus standard induction chemotherapy for treating adult acute leukemia (AL). We randomly assigned 332 patients wit...
We assessed the clinical effectiveness and safety of CKI (compound Kushen injection) plus standard induction chemotherapy for treating adult acute leukemia (AL). We randomly assigned 332 patients with newly diagnosed AL to control (n = 165, receiving DA (daunorubicin and cytarabine) or hyper-CVAD (fractionated cyclophosphamide, doxorubicin, vincristine, and dexamethasone)) or treatment (n = 167, receiving CKI and DA or hyper-CVAD) groups. Posttreatment, treatment group CD3+, CD4+, CD4+/CD8+, natural killer (NK) cell, and immunoglobulin (IgG, IgA, and IgM) levels were significantly higher than those of the control group (p < 0.05), and CD8+ levels were lower in the treatment group than in the control group (p < 0.05). Treatment group interleukin- (IL-) 4 and IL-10 levels were significantly higher compared to the control posttreatment (both p < 0.05) as were complete remission, overall response, and quality of life (QoL) improvement rates (p < 0.05). The control group had more incidences of grade 3/4 hematologic and nonhematologic toxicity (p < 0.05). Responses to induction chemotherapy, QoL improvement, and adverse events incidence between control group patients with acute myeloid leukemia and acute lymphocytic leukemia were not significantly different. CKI plus standard induction chemotherapy is effective and safe for treating AL, possibly by increasing immunologic function.
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- Expression of CD56 is a risk factor for acute lymphocytic leukemia with central nervous system involvement in adults. [Journal Article]
- HHematology 2016 Oct 13; :1-7
- CONCLUSIONS: CD56 expression should be regarded as an independent risk factor for ALL with CNS involvement in adults.