Compound Kushen Injection suppresses multiple myeloma progression via TOP1-targeted coordination of DNA damage and endoplasmic reticulum stress.

Background: Multiple myeloma (MM) is a plasma cell malignancy that remains incurable due to inevitable relapse and poor treatment tolerance. Compound Kushen Injection (CKI), a traditional Chinese medicinal formulation, has been reported to exert anti-tumor effects in various cancers, but its efficacy and mechanisms in MM remain unclear.

Purpose: This study aimed to elucidate the anti-MM mechanisms of CKI, focusing on its induction of DNA damage response (DDR) and endoplasmic reticulum (ER) stress, and to assess synergy with proteasome inhibitors (PIs).

MMP14 from BM-MSCs facilitates progression and Ara-C resistance in acute myeloid leukemia via the JAK/STAT pathway.

Growing evidence underscores the pivotal impact of crosstalk between leukemic stem cells (LSCs) and mesenchymal stromal cells (MSCs) within their niche on leukemia initiation, progression, and therapy response. Although MMP14 plays an important role in inflammation and cancer, the regulation and role of MSC-derived MMP14 in acute myeloid leukemia (AML) are largely unknown. Here, we found that AML patient-derived MSCs (AML-MSCs) were more supportive of AML cell growth compared to healthy donor-derived MSCs (HD-MSCs).

Multi-Omic Analysis Reveals the Impact of Bortezomib in Hyperleukocytic Acute Myeloid Leukemia.

Background: Hyperleukocytic acute myeloid leukemia (HL-AML) is associated with early complications and high mortality rates, highlighting the urgent need for more effective therapeutic strategies.

Methods: This study conducted label-free proteomic analysis on serum from HL-AML and non-HL AML (NHL-AML) patients, integrating the data with the OHSU transcriptomic database. Flow cytometry was used to evaluate the in vitro impact of bortezomib.

Clinical and immunological characteristics of high-risk double-hit multiple myeloma.

At present, the characteristics of double-hit multiple myeloma (DHMM) are unknown. We retrospectively analyzed the clinical data from 433 new diagnosed MM patients and found that DHMM have a higher β2-MG level and percentage of bone marrow plasma cell. Cox regression analysis showed that the prognosis of DHMM was not limited by clinical indicators.

FLT3-selective PROTAC: Enhanced safety and increased synergy with Venetoclax in FLT3-ITD mutated acute myeloid leukemia.

Acute myeloid leukemia (AML) patients carrying Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations often face a poor prognosis. While some FLT3 inhibitors have been used clinically, challenges such as short efficacy and poor specificity persist. Proteolytic targeting chimera (PROTAC), with its lower ligand affinity requirement for target proteins, offers higher and rapid targeting capability.

Integrated bioinformatic analysis of mitochondrial metabolism-related genes in acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is a common hematologic malignancy characterized by poor prognoses and high recurrence rates. Mitochondrial metabolism has been increasingly recognized to be crucial in tumor progression and treatment resistance. The purpose of this study was to examined the role of mitochondrial metabolism in the immune regulation and prognosis of AML.

CAR T-Cell Immunotherapy Treating T-ALL: Challenges and Opportunities.

T-cell acute lymphoblastic leukemia (T-ALL), a form of T-cell malignancy, is a typically aggressive hematological malignancy with high rates of disease relapse and a poor prognosis. Current guidelines do not recommend any specific treatments for these patients, and only allogeneic stem cell transplant, which is associated with potential risks and toxicities, is a curative therapy. Recent clinical trials showed that immunotherapies, including monoclonal antibodies, checkpoint inhibitors, and CAR T therapies, are successful in treating hematologic malignancies.

The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity.

CAR T-cell therapy is well tolerated and effective in patients with Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). However, even second- generation anti-CD30 CAR T-cells with CD28 (28z) costimulatory domains failed to achieve the desired rate of complete responses. In the present study, we developed second-generation (CD28z) and third-generation (CD28BBz) CAR T-cells targeting CD30 and investigated their efficacy in vitro and in vivo.

Interphase Fluorescence in situ Hybridization of Bone Marrow Smears of Multiple Myeloma.

Fluorescence in situ hybridization (FISH) detection is an indispensable method in genetic risk stratification in multiple myeloma (MM), which is one of the most common hematological malignancies. The identifying characteristic of MM is accumulated malignant plasma cells in bone marrow. FISH reports for MM mainly focus on purified or identified clonal plasma cells, rather than all nucleated cells, by sorting with anti-CD138 magnetic beads or marking with cytoplasmic immunoglobulin light chain κ or λ.

Therapeutic Plateletpheresis in Patients With Thrombocytosis: Gender, Hemoglobin Before Apheresis Significantly Affect Collection Efficiency.

Thrombocytosis is a common symptom in myeloproliferative neoplasms (MPN), and excessive proliferation may deteriorate into thrombosis, bleeding, myelofibrosis, and may ultimately convert to acute leukemia. This study aimed to investigate the collection efficiency of plateletpheresis (CEPP) and factors influencing its efficacy in patients with thrombocytosis. From September 2010 to December 2016, 81 patients from two institutions in China with myeloproliferative neoplasms and thrombocytosis accompanied by severe symptoms were treated with plateletpheresis by Fresenius COM.

Evaluation of prognostic staging systems of multiple myeloma in the era of novel agents.

This study aimed to evaluate the existing staging systems for multiple myeloma (MM) in the real world. From January 2010 to June 2019, we retrospectively analyzed 859 newly diagnosed MM patients from two institutions. Clinical data including laboratory findings, imaging examinations and staging system were obtained by reviewing medical records.

CAR T cells targeting CD99 as an approach to eradicate T-cell acute lymphoblastic leukemia without normal blood cells toxicity.

CAR T cell therapy has shown dramatic clinical success in relapsed or refractory B-ALL and other hematological malignancies. However, the loss of specific antigens, cell fratricide, T cell aplasia, and normal T cell separation are challenges in treating T cell leukemia/lymphoma with CAR T therapy. CD99 is a promising antigen to target T-ALL and AML as it is strongly expressed on the majority of T-ALL and AML.

Antiproliferative and Immunoregulatory Effects of Azelaic Acid Against Acute Myeloid Leukemia the Activation of Notch Signaling Pathway.

Acute myeloid leukemia (AML) is a common type of hematological malignancy that can progress rapidly. AML has a poor prognosis and a high incidence of relapse due to therapeutic resistance. Azelaic acid (AZA), a small molecular compound is known to exhibit antitumor effect on various tumor cells.

A Retrospective Analysis: A Novel Index Predicts Survival and Risk-Stratification for Bone Destruction in 419 Newly Diagnosed Multiple Myelomas.

Objective: Multiple myeloma (MM) patients with bone destruction are difficult to restore, so it is of great clinical significance to further explore the factors affecting MM bone destruction.

Methods And Results: This study retrospectively analyzed 419 cases with MM. Multiple linear regression analysis showed that those MM patients with a higher concentration of Ca in serum, higher positive rate of CD138 immuno-phenotype and advanced in stage with 13q34 deletion in cytogenetics would be more prone to bone destruction, while total bile acid (TBA) and kappa chain isotope negatively correlated with bone destruction in MM patients.

The novel thioredoxin reductase inhibitor A-Z2 triggers intrinsic apoptosis and shows efficacy in the treatment of acute myeloid leukemia.

Chemoresistance and high incidence of relapse in acute myeloid leukemia (AML) patients are associated with thioredoxin (Trx) overexpression. Thus, targeting the Trx system has emerged as a promising approach to treating AML. Both arsenicals and azelaic acid (AZA) are thioredoxin reductase (TrxR) inhibitors and possess antileukemic effects.