Journal: Current Issues in Molecular Biology

Article Title: FLT3 and IRAK4 Inhibitor Emavusertib in Combination with BH3-Mimetics in the Treatment of Acute Myeloid Leukemia

doi: 10.3390/cimb46040184

Figure Lengend Snippet: Schematic presentation of the FLT3 and SCFR (CD117, c-KIT) as well as IL1R and TLR4 signaling pathways and downstream effects. FLT3-ITD and FLT3-TKD are constitutively active growth factor receptors. SCFR (c-KIT) is an inducible growth factor receptor activated by stem cell factor (SCF). Both tyrosine receptor kinases activate PI3K-AKT, RAS-MEK-ERK, and STAT5, leading to cell growth and proliferation via inhibition of the tumor suppressor TP53 and induction of the apoptosis regulators MCL1 and BCL2. IL1R and TLR4 are inducible receptors signaling via MyD88 and IRAK4. HSP90 protein can bind and stabilize client proteins, including AKT, BCL2, FLT3, JAK, MDM2, STAT5, SHP2, and BRAF. Hsp90 proteins are indicated in yellow, oncogenic protein functions in red, tumor suppressor functions in green ovals, and targeted inhibitors in blue rectangles. Sharp arrows and blunt arrows indicate target induction and inhibition, respectively.

Article Snippet: Human AML cell lines OCI-AML3 (AML-M4, FLT3 wt, DNMT3A R882C, NPM1 mut, TP53 wt), MOLM-13 (AML-M5, t (9;11), FLT3 -ITD, TP53 wt), SKM-1 (AML-M5, FLT3 wt, TP53 mut), and ML-2 (AML-M4, t (6;11), FLT3 wt, TP53 wt) cells were supplied by the Leibniz Institute DSMZ, German Collection of Microorganisms and Cell Cultures.

Techniques: Protein-Protein interactions, Inhibition

Journal: Current Issues in Molecular Biology

Article Title: FLT3 and IRAK4 Inhibitor Emavusertib in Combination with BH3-Mimetics in the Treatment of Acute Myeloid Leukemia

doi: 10.3390/cimb46040184

Figure Lengend Snippet: Clinical characteristics of primary AML cells.

Article Snippet: Human AML cell lines OCI-AML3 (AML-M4, FLT3 wt, DNMT3A R882C, NPM1 mut, TP53 wt), MOLM-13 (AML-M5, t (9;11), FLT3 -ITD, TP53 wt), SKM-1 (AML-M5, FLT3 wt, TP53 mut), and ML-2 (AML-M4, t (6;11), FLT3 wt, TP53 wt) cells were supplied by the Leibniz Institute DSMZ, German Collection of Microorganisms and Cell Cultures.

Techniques: Mutagenesis

Journal: Cell Death Discovery

Article Title: Novel meriolin derivatives potently inhibit cell cycle progression and transcription in leukemia and lymphoma cells via inhibition of cyclin-dependent kinases (CDKs)

doi: 10.1038/s41420-024-02056-6

Figure Lengend Snippet: A Cytotoxicity was determined after 24 h with increasing concentrations of meriolin 16 and meriolin 36 in two myeloid cell lines (K562 (chronic myeloid leukemia; CML) and HL60 (acute myeloid leukemia; AML)) and six lymphoid cell lines (SUPB15 (B cell acute lymphoblastic leukemia; B-ALL), KOPTK1 (T-ALL), HPBALL (T cell acute lymphoblastic leukemia; T-ALL), MOLT4 (T-ALL), Ramos (Burkitt B cell lymphoma) and Jurkat (acute T cell lymphoblastic leukemia; T-ALL)). Cell viability was assessed by AlamarBlue® viability assay. Error bars = Mean ± SD of a representative experiment performed in triplicates. B Cytotoxicity was determined after 24 h with increasing concentrations of meriolin 16 and meriolin 36 in malignant primary patient cells such as diffuse large B cell lymphoma cells (DLBCL), follicular lymphoma cells (FL) and chronic lymphocytic leukemia cells (CLL) by AlamarBlue® assay. Error bars = Mean ± SD of a representative experiment performed in triplicates. The respective IC 50 values are given on the right side for the respective compound in each cell line. n.d. = not detected in the depicted concentration range.

Article Snippet: HeLa cells (human cervix carcinoma; #ACC-57), HL60 (human acute myeloid leukemia; #ACC-3), HPBALL (human T cell acute lymphoblastic leukemia; #ACC-483), MOLT4 (human T cell acute lymphoblastic leukemia; #ACC-362), K562 (human chronic myeloid leukemia; #ACC-10) and SUPB15 (human B cell acute lymphoblastic leukemia; #ACC-389) were obtained from DSMZ.

Techniques: Viability Assay, Alamar Blue Assay, Concentration Assay