Olverembatinib combined with venetoclax and reduced-intensity chemotherapy for adult newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a single-center, single-arm, phase 2 trial.

Tyrosine kinase inhibitors (TKIs) combined with chemotherapy and immunotherapy evolved as the standard treatment for newly diagnosed (ND) Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph ALL). Nonetheless, the efficacy and safety of combining TKIs with BCL-2 inhibitors in ND Ph ALL have yet to be fully elucidated. Hence, we carried out a prospective clinical trial to explore the efficacy and safety of olverembatinib combined with venetoclax and reduced-intensity chemotherapy as frontline treatment in Ph ALL.

Treatment of pro-B acute lymphoblastic leukemia and severe plaque psoriasis with anti-CD19 CAR T cells: a case report.

We report on a rare case of adult pro-B acute lymphoblastic leukemia (pro-B ALL) accompanied with severe refractory plaque psoriasis treated using autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. An 18-year-old man with a known history of mild plaque psoriasis for 1 year was diagnosed with pro-B ALL. After induction chemotherapy, his psoriasis began to worsen.

A novel fusion protein TBLR1-RARα acts as an oncogene to induce murine promyelocytic leukemia: identification and treatment strategies.

Acute promyelocytic leukemia (APL) is characterized by a specific chromosome translocation involving RARα and its fusion partners. For decades, the advent of all-trans retinoic acid (ATRA) synergized with arsenic trioxide (AsO) has turned most APL from highly fatal to highly curable. TBLR1-RARα (TR) is the tenth fusion gene of APL identified in our previous study, with its oncogenic role in the pathogenesis of APL not wholly unraveled.

RUNX1 inhibits proliferation and induces apoptosis of t(8;21) leukemia cells KLF4-mediated transactivation of P57.

RUNX1 is a key transcription factor in hematopoiesis and its disruption is one of the most common aberrations in acute myeloid leukemia. RUNX1 alterations affect its DNA binding capacity and transcriptional activities, leading to the deregulation of transcriptional targets, and abnormal proliferation and differentiation of myeloid cells. Identification of RUNX1 target genes and clarification of their biological functions are of great importance in the search for new therapeutic strategies for RUNX1-altered leukemia.

Identification of JL1037 as a novel, specific, reversible lysine-specific demethylase 1 inhibitor that induce apoptosis and autophagy of AML cells.

Lysine-specific demethylase 1 (LSD1) has been recognized as a potential therapeutic target for acute myeloid leukemia (AML). Herein, we identified a novel LSD1 inhibitor, JL1037, via Computer Aided Drug Design technology. JL1037 is a potent, selective and reversible LSD1 inhibitor with IC50s of 0.

FHL2 interacts with iASPP and impacts the biological functions of leukemia cells.

iASPP is an inhibitory member of apoptosis-stimulating proteins of p53 (ASPP) family, which inhibits p53-dependent apoptosis. iASPP was highly expressed in acute leukemia, inhibited leukemia cells apoptosis and promoted leukemogenesis. In order to clarify its mechanism, a yeast two-hybrid screen was performed and FHL2 was identified for the first time as one of the binding proteins of iASPP.

Rac1 GTPase Promotes Interaction of Hematopoietic Stem/Progenitor Cell with Niche and Participates in Leukemia Initiation and Maintenance in Mouse.

Interaction between hematopoietic stem/progenitor cells (HSPCs) with their niche is critical for HSPC function. The interaction also plays an important role in the multistep process of leukemogenesis. Rac1 GTPase has been found to be highly expressed and activated in leukemia patients.

[Effect of TBLR1-RARα Fusion Gene on Erythroid Differentiation of K562 Cells].

Objective: To explore the effects of TBLR1-RARα on the differentiation induction of leukemia cell line K562 cells into erythroid lineage and to investigate its related mechanisms.

Methods: Tet-Off inducible system was used to construct the conditional expression vector of TBLR1-RARα fusion gene by cloning the TBLR1-RARα fragment into lentivirus vector pLVX-Tight-Puro, the expression of TBLR1-RARα fusion gene was induced by doxycycline (Dox). Then, K562 cells were transfected with lentivirus pLVX-Tight-Puro-TBLR1-RARα-flag, and the expression of fusion proteins was verified by Western blot.

Up-regulated A20 promotes proliferation, regulates cell cycle progression and induces chemotherapy resistance of acute lymphoblastic leukemia cells.

A20, also known as tumor necrosis factor-α (TNFα)-induced protein 3 (TNFAIP3), has been identified as a key regulator of cell survival in many solid tumors. However, little is known about the protein expression level and function of A20 in acute lymphoblastic leukemia (ALL). In this study, we found that A20 is up-regulated in ALL patients and several cell lines.

A novel SAHA-bendamustine hybrid induces apoptosis of leukemia cells.

Hybrid anticancer drugs are of great therapeutic interests as they can potentially overcome the deficiencies of conventional chemotherapy drugs and improve the efficacy. Many studies have revealed that the combination of histone deacetylase inhibitors (HDACi) and alkylating agents have synergistic effects. We reported a novel hybrid NL-101, in which the side chain of bendamustine was replaced with the hydroxamic acid of HDACi vorinostat (SAHA).

[Silence potentiates chemosensitivity of K562 cells to SAHA].

Ribosomal protein S27a (RPS27a) can perform extra-ribosomal functions besides imparting a role in ribosome biogenesis and post-translational modifications of proteins. The RPS27a gene has been reported to be over-expressed in breast fibroadenomas, colorectal and renal cancers, advanced-phase chronic myeloid leukemia (CML) and acute leukemia (AL) patients. This study was purposed to explore the function of RPS27a in CML-erythroleukemia cell line K562 cells.

TBLR1 fuses to retinoid acid receptor α in a variant t(3;17)(q26;q21) translocation of acute promyelocytic leukemia.

The majority of acute promyelocytic leukemia (APL) cases are characterized by the PML-RARα fusion gene. Although the PML-RARα fusion gene can be detected in >98% of APL cases, RARα is also found to be fused with other partner genes, which are also related to all-trans retinoic acid (ATRA)-dependent transcriptional activity and cell differentiation. In this study, we identified a novel RARα fusion gene, TBLR1-RARα (GenBank KF589333), in a rare case of APL with a t(3;17)(q26;q21),t(7;17)(q11.