Single-cell transcriptome profiling reveals blast cell heterogeneity and identifies novel therapeutic target IKZF2 in t(8;21) acute myeloid leukaemia.

The t(8;21)(q22;q22) translocation is one of the most recurrent cytogenetic aberrations in acute myeloid leukaemia (AML). While most patients achieve complete remission, approximately 40% of them still relapse. Early identification and elimination of leukaemia clones with relapse potential could improve prognosis for t(8;21) AML patients.

CD7 CAR-T therapy: current developments, improvements, and dilemmas.

Chimeric antigen receptor (CAR) T-cell therapy is an epoch-making immunotherapy for the treatment of relapsed or refractory (r/r) blood tumors, as demonstrated by its successful implementation in r/r B cell-derived malignancies. However, replicating this success in T-cell leukemia or lymphoma remains challenging. Among the various potential target antigens, CD7 has garnered attention as a promising candidate.

Novel loop structure of human IgG1 Fc fused CD38 targeted bispecific antibodies and their anti-tumor effect in acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) still lacks an ideal immunotherapy target. CD38 serves as a potential therapeutic target for AML. Classical bispecific antibody (BsAb) requires continuous infusion due to small molecular size and short half-life.

The critical role of DNA damage-inducible transcript 4 (DDIT4) in stemness character of leukemia cells and leukemia initiation.

Leukemia stem cells (LSCs) are critical for leukemia initiation, and the stemness properties of LSCs are related to disease relapse. Stemness properties, including quiescence, self-renewal, and chemoresistance, are maintained through an interplay between leukemia cells and the bone marrow (BM) niche. Here, we demonstrated that DNA damage-inducible transcript 4 (DDIT4) can be induced in a hypoxic BM niche and is required for the quiescence and self-renewal of AML1-ETO9a (AE9a)-transformed leukemia cells in vitro.

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.

AML1-ETO and CCND2 overexpression cooperate to drive acute myeloid leukemia initiation and progression.

Increasing numbers of clinical cohorts have detected CCND2 mutations in acute myeloid leukemia, especially in the subtype of acute myeloid leukemia with the t(8;21) translocation. This acute myeloid leukemia subtype is characterized by the formation of the AML1-ETO fusion gene. However, the AML1-ETO fusion gene alone is not sufficient to drive leukemia development.

Measurable residual disease recurrence as early warning of relapse in acute myeloid leukemia.

To investigate the clinical features and outcomes of measurable residual disease recurrence (MRD-R) by multiparameter flow cytometric in acute myeloid leukemia (AML). We retrospectively analyzed clinical characteristic, residual disease status and outcomes of 767 newly diagnosed AML patients achieving complete remission within two cycles of induction at our center. Totally, 171 (22.

Nanomaterials in stimulus-responsive drug delivery systems facilitate precise therapy for hematologic diseases.

Stimulus-responsive drug delivery systems (SRDDS) are advanced mechanisms that release drugs in response to specific bodily microenvironments or signal receptors, triggering targeted physiological reactions. These systems integrate the chemical properties of drugs with the organism's environment and immune response, modulating the metabolic and growth conditions of target cells or organs to exert therapeutic effects. Initially focused on anti-inflammatory and antioxidant functions enzymes like SOD and CAT, SRDDS have evolved with advancements in tumor microenvironment research and bioinformatics, becoming a cornerstone for precision medicine and solid tumor treatment.

Advances in RARα fusion genes in acute promyelocytic leukemia.

Retinoic acid receptor α (RARα) is a ligand-dependent transcription factor that dimerizes with retinoid X receptor α (RXRα) to activate target gene promoters, playing a critical role in normal hematopoiesis and granulocyte differentiation. The translocation of chromosomes 15 and 17 generates the promyelocytic leukemia-retinoic acid receptor α (PML-RARα) fusion gene, the master driver of acute promyelocytic leukemia (APL). The PML-RARα oncoprotein exerts two major effects: transcriptional repression and disruption of promyelocytic leukemia (PML) function.

Clinical characteristics and therapeutic determinants of differ from those of acute myeloid leukemia.

Core binding factor acute myeloid leukemia (CBF-AML) includes RUNX1::RUNX1T1 and CBFB::MYH11 AML. To investigate whether they should be regarded as distinct entities and treated separately, we retrospectively analyzed 536 patients with CBF-AML aged 60 years or younger. For CBFB::MYH11 AML, no outcome differences were observed between standard-dose (SD) and intermediate-dose (ID) cytarabine induction, with 5-year overall survival (OS) and relapse-free survival (RFS) at 86.

Prognostic impact of co-mutations in adults with -mutated acute myeloid leukemia.

Acute myeloid leukemia (AML) is characterized by the accumulation of cytogenetic and molecular abnormalities. Isocitrate dehydrogenase 1 and 2 () mutations occur in 11% to 20% of adults with AML. The outcome of -mutated AML is heterogeneous and affected by co-mutational patterns.

Dynamin2 mutations in newly diagnosed acute myeloid leukemia: clinical characteristics, and prognostic significance.

Acute myeloid leukemia (AML) is a highly heterogeneous myeloid malignancy which can be classified by genetic aberrations. To evaluate the impact of the dynamin 2 mutation in AML, we systematically assessed the characteristics and prognostic of DNM2 mutated patients in AML. In 912 AML patients, 20 somatic mutations in the DNM2 gene were identified among the 18 DNM2 mutated AML patients (2%).

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.

The Clinical and Molecular Characterization of Distinct Subtypes in Adult T Cell Acute Lymphoblastic Leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is a clonal proliferative malignant disease characterized by abnormal T-cell development. The classification of T-ALL primarily hinges on immunophenotype, encompassing early T-cell precursor (ETP)-ALL, near-ETP-ALL, and non-ETP-ALL. We summarized clinical information from 117 patients, with genetic data available for 77 patients and transcriptomic data available for 24 patients.

U2AF1 mutation causes an oxidative stress and DNA repair defect in hematopoietic and leukemic cells.

U2AF1 is a core component of spliceosome and controls cell-fate specific alternative splicing. U2AF1 mutations have been frequently identified in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients, and mutations in U2AF1 are associated with poor prognosis in hematopoietic malignant diseases. Here, by forced expression of mutant U2AF1 (U2AF1 S34F) in hematopoietic and leukemic cell lines, we find that U2AF1 S34F causes increased reactive oxygen species (ROS) production.

Loop33 × 123 CAR-T targeting CD33 and CD123 against immune escape in acute myeloid leukemia.

Background: Immunotherapy, such as chimeric antigen receptor T (CAR-T) cells targeting CD33 or CD123, has been well developed over the past decade for the treatment of acute myeloid leukemia (AML). However, the inability to sustain tumor-free survival and the possibility of relapse due to antigen loss have raised concerns. A dual targeting of CD33 and CD123 is needed for better outcomes.

Risk stratification in the clinical application of minimal residual disease assessment in acute myeloid leukemia.

Background: In acute myeloid leukemia (AML), further investigation is warranted to integrate measurable residual disease (MRD) with genetic characteristics for formulating a dynamic prognostic system for predicting response and selecting appropriate postremission therapeutic strategies.

Methods: The authors incorporated MRD with genetic risk classification and assessed its impact on transplantation decision making within different risk cohorts, comprising 769 patients with newly diagnosed AML across three clinical trials. Only patients who achieved complete remission (CR) within two courses of chemotherapy were selected.

Targeting Fatty Acid Metabolism Abrogates the Differentiation Blockade in Preleukemic Cells.

Metabolism plays a key role in the maintenance of normal hematopoietic stem cells (HSC) and in the development of leukemia. A better understanding of the metabolic characteristics and dependencies of preleukemic cells could help identify potential therapeutic targets to prevent leukemic transformation. As AML1-ETO, one of the most frequent fusion proteins in acute myeloid leukemia that is encoded by a RUNX1::RUNX1T1 fusion gene, is capable of generating preleukemic clones, in this study, we used a conditional Runx1::Runx1t1 knockin mouse model to evaluate preleukemic cell metabolism.

Mitochondrial genetic variations in leukemia: a comprehensive overview.

Leukemias are a group of heterogeneous hematological malignancies driven by diverse genetic variations, and the advent of genomic sequencing technologies facilitates the investigation of genetic abnormalities in leukemia. However, these sequencing-based studies mainly focus on nuclear DNAs. Increasing evidence indicates that mitochondrial dysfunction is an important mechanism of leukemia pathogenesis, which is closely related to the mitochondrial genome variations.

Identifying ADGRG1 as a specific marker for tumor-reactive T cells in acute myeloid leukemia.

Besides chemotherapy and hematopoietic stem cell transplantation (HSCT), autologous T cells can also serve as a new treatment approach for AML patients. However, the features of tumor-reactive T cells and their distinctive markers still lack full description. To evaluate the characteristics of tumor-reactive T cells, we collected bone marrow (BM) T cells from newly diagnosed AML patients with RUNX1::RUNX1T1 as examples for paired single-cell RNA sequencing and single-cell V(D)J sequencing.

A dual-targeting approach with anti-IL10R CAR-T cells engineered to release anti-CD33 bispecific antibody in enhancing killing effect on acute myeloid leukemia cells.

Background: Immunotherapies, including chimeric antigen receptor (CAR) T cells and bispecific antibodies (BsAbs), encounter several challenges in the management of acute myeloid leukemia (AML), including limited persistence of these treatments, antigen loss and resistance of leukemia stem cells (LSCs) to therapy.

Methods: Here, we proposed a novel dual-targeting approach utilizing engineered anti-IL10R CAR-T cells to secrete bispecific antibodies targeting CD33. This innovative strategy, rooted in our previous research which established a connection between IL-10 and the stemness of AML cells, designed to improve targeting efficiency and eradicate both LSCs and AML blasts.