Gene expression of ASNS, LGMN and CTSB is elevated in a subgroup of childhood BCP-ALL with PAX5 deletion.
Gene expression of ASNS, LGMN and CTSB is elevated in a subgroup of childhood BCP-ALL with PAX5 deletion. Oncol Lett. 2019 Dec;18(6):6926-6932 Authors: Wrona E, Jakubowska J, Pawlik B, Pastorczak A, Madzio J, Lejman M, Sędek Ł, Kowalczyk J, Szczepański T, Młynarski W Abstract Resistance to L-asparaginase (L-asp) is a major contributor to poor treatment outcomes of several subtypes of childhood B cell precursor acute lymphoblastic leukemia (BCP-ALL). Asparagine synthetase (ASNS), legumain (LGMN) and cathepsin B (CTSB) serve a key role in L-asp resistance. The association between genetic subtypes of BCP-ALL and the expression of ASNS, LGMN and CTSB may elucidate the mechanisms of treatment failure. Bone marrow samples of 52 children newly diagnosed with BCP-ALL were screened for major genetic abnormalities and ASNS, LGMN and CTSB gene expression levels. The cohort was further divided into groups corresponding to the key genetic aberrations occurring in BCP-ALL: Breakpoint cluster region and Abelson murine leukemia viral oncogene homolog 1 fusion; hyperdiploidy, hypodiploidy, ETS variant 6 and runt-related transcription factor 1 fusion and other BCP-ALL with no primary genetic aberration identified. A subgroup analysis based on the differences in copy number variations demonstrated a significant increase of ASNS, LGMN and CTSB median expression in other BCP-ALL cases with paired box 5 (PAX5) deletion (P=0.0117; P=0.0036; P
ConclusionWe have demonstrated that PP is a novel therapeutic lead compound that counteracts the respiratory reprogramming found in refractory ALL cells and can be effectively formulated into a nanoparticle delivery system to target the BTME.
Leukemia, Published online: 27 January 2020; doi:10.1038/s41375-020-0715-2Disease escape with the selective loss of the Philadelphia chromosome after tyrosine kinase inhibitor exposure in Ph-positive acute lymphoblastic leukemia
Chidamide induces necroptosis via regulation of c‑FLIPL expression in Jurkat and HUT‑78 cells. Mol Med Rep. 2020 Feb;21(2):936-944 Authors: Chi Z, Gao H, Liu H, Wu B, Zhang B, Gu M, Yang W Abstract T‑cell acute lymphoblastic leukemia (T‑ALL) is a hematopoietic malignancy, which is associated with a poor prognosis. It is difficult to achieve complete remission or long‑term survival with conventional chemotherapy, partly due to decreased apoptosis. However, necroptosis can serve as an alternative pathway to induce cell death. The present study investigated whether the selective histone deacetyl...
This study demonstrates the important effects of glycosylation on L-ASNase properties and opens up new possibilities to use glycosylated L-ASNases for the treatment of ALL.
For patients with refractory or high-risk hematologic malignancies, like acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and acute lymphoblastic leukemia (ALL), allogeneic hematopoietic stem cell transplant (Allo-HSCT) is a potentially curative approach. Morbidities and mortality associated with current conditioning regimens limit the use of this curative procedure. As a result, many eligible patients do not consider transplant and 2/3 of those transplanted are only able to tolerate a reduced intensity conditioning regimen, which is associated with increased relapse rates (Scott, J Clin Onc 2017).
Patients (pts) receiving CTL019 (tisagenlecleucel) for B-ALL with high tumor burden (HTB) are at high risk for developing severe CRS. Tocilizumab, an IL-6 receptor antibody, is a vital component of severe CRS management; however, its role in preventing severe CRS is not known. We sought to determine the effectiveness of preemptive tocilizumab (PT) administration in decreasing the rate of grade (gr) 4 CRS in HTB pts.
Chimeric antigen receptor T cell (CAR-T cell) therapy has become a promising treatment for children with acute lymphoblastic leukaemia (ALL) and Non-Hodgkin lymphoma (NHL). Cytokine release syndrome (CRS) and Immune effector cell associated neurotoxicity syndrome (ICANS) are well-documented serious side-effects of CAR-T cell therapy, and early recognition, intervention and aggressive supportive therapy is paramount.Tociluzimab is the mainstay of treatment for moderate to severe CRS, with early administration essential.
Transplant outcomes for patients with acute lymphoblastic leukemia (ALL) after haploidentical hematopoietic cell transplantation (haploHCT) with post-transplant cyclophosphamide (PTCy) compared to an HLA matched unrelated donors (MUD) transplantation are unknown. We, therefore retrospectively compared outcomes of 487 patients with ALL who underwent haploHCT with PTCy, reported from the participating centers (TCT-RC and EBMT) from 01/2005 to 06/2018, with a matched cohort of 974 patients (1:2 ratio) who underwent MUD-HCT and were reported to the EBMT. Patients were matched for sex, disease stage (CR1, CR2, other), di...
CD19 directed chimeric antigen receptor T cell (CART19) therapy has shown remarkable activity in B cell lymphoma and acute lymphoblastic leukemia (ALL). With the emergence of therapeutic anti CD19 antibodies for the treatment of B cell malignancies, it remains to be elucidated whether such antibodies would interfere with the ability of CART19 to exert their antitumor effect in a subsequent therapy.Tafasitamab is an Fc enhanced humanized anti CD19 monoclonal antibody which mediates antibody dependent cellular toxicity (ADCC), antibody dependent cellular phagocytosis and direct cytotoxicity.