Mechanisms of resistance to targeted therapies for relapsed or refractory acute myeloid leukemia

Kropp, Erin M.; Li, Qing

doi:10.1016/j.exphem.2022.04.001

Cited by 7 publications

(4 citation statements)

References 133 publications

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“…Splicing factors are essential to pre-mRNA regulation in normal cellular functions. Mutations of two such factors in SRSF2 and U2AF1 have been identified as high molecular risk mutations in myelofibrosis as both are associated with lower median overall survival compared with wildtype [ 49 , 66 , 67 ]. Both SRSF2 and U2AF1 mutations are rare in polycythemia vera (both < 2%) and essential thrombocythemia (collectively 1–3% as shown in Table 1 ) [ 13 , 15 ].…”

Section: Mutations In Splicing Factorsmentioning

confidence: 99%

“…Isocitrate dehydrogenase ( IDH ) normally catalyzes the conversion of isocitrate to alpha-ketoglutarate and in mammals, both isoenzymes IDH1 (cytosolic) and IDH2 (mitochondrial) are NADP-dependent [ 66 , 71 ]. Mutant IDH1/2 in leukemic cells instead yields a separate oncometabolite called 2-hydroxyglutarate (2-HG), leading to multiple effects that include hematopoietic differentiation and inhibition of the TET methylcytosine dioxygenases, which are instrumental in DNA demethylation [ 67 ]. IDH mutations have been identified (and are targeted) in numerous solid and hematologic neoplasms, including acute myeloid leukemia, cholangiocarcinoma, and glioma [ 72 ].…”

Section: Mutations In Idh-regulators Of Cellular Metabolismmentioning

confidence: 99%

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Exploring the Molecular Landscape of Myelofibrosis, with a Focus on Ras and Mitogen-Activated Protein (MAP) Kinase Signaling

Reynolds,

Pettit,

Kandarpa

et al. 2023

Cancers

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Myelofibrosis (MF) is a clonal myeloproliferative neoplasm (MPN) characterized clinically by cytopenias, fatigue, and splenomegaly stemming from extramedullary hematopoiesis. MF commonly arises from mutations in JAK2, MPL, and CALR, which manifests as hyperactive Jak/Stat signaling. Triple-negative MF is diagnosed in the absence of JAK2, MPL, and CALR but when clinical, morphologic criteria are met and other mutation(s) is/are present, including ASXL1, EZH2, and SRSF2. While the clinical and classic molecular features of MF are well-established, emerging evidence indicates that additional mutations, specifically within the Ras/MAP Kinase signaling pathway, are present and may play important role in disease pathogenesis and treatment response. KRAS and NRAS mutations alone are reportedly present in up to 15 and 14% of patients with MF (respectively), and other mutations predicted to activate Ras signaling, such as CBL, NF1, BRAF, and PTPN11, collectively exist in as much as 21% of patients. Investigations into the prevalence of RAS and related pathway mutations in MF and the mechanisms by which they contribute to its pathogenesis are critical in better understanding this condition and ultimately in the identification of novel therapeutic targets.

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Section: Mutations In Splicing Factorsmentioning

confidence: 99%

Section: Mutations In Idh-regulators Of Cellular Metabolismmentioning

confidence: 99%

Exploring the Molecular Landscape of Myelofibrosis, with a Focus on Ras and Mitogen-Activated Protein (MAP) Kinase Signaling

Reynolds,

Pettit,

Kandarpa

et al. 2023

Cancers

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“…As an aggressive blood malignancy, AML is marked by the accumulation of immature blood cells, which severely interferes with the normal hematopoietic system. The 5-year survival rate is approximately 30%; therefore, developing novel targeted therapies or treatments has become an important research focus [ 2 – 4 ]. Global Burden Disease reported that the incidence of AML increased from 63,840 to in 1990 to 119,570 in 2017 [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Recent advance in phytonanomedicine and mineral nanomedicine delivery system of the treatment for acute myeloid leukemia

et al. 2023

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Acute myeloid leukemia (AML) is an invasive hematopoietic malignancy caused by excessive proliferation of myeloblasts. Classical chemotherapies and cell transplantation therapies have remarkable efficacy in AML treatment; however, 30–40% of patients relapsed or had refractory disease. The resistance of AML is closely related to its inherent cytogenetics or various gene mutations. Recently, phytonanomedicine are found to be effective against resistant AML cells and have become a research focus for nanotechnology development to improve their properties, such as increasing solubility, improving absorption, enhancing bioavailability, and maintaining sustained release and targeting. These novel phytonanomedicine and mineral nanomedicine, including nanocrystals, nanoemulsion, nanoparticles, nanoliposome, and nanomicelles, offer many advantages, such as flexible dosages or forms, multiple routes of administration, and curative effects. Therefore, we reviewed the application and progress of phytomedicine in AML treatment and discussed the limitations and future prospects. This review may provide a solid reference to guide future research on AML treatment.

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“…Although targeted drugs have improved the survival rate of patients with FLT3 -mutated AML [ 3 ], additional mutations driving resistance have emerged, resulting in short response and survival durations [ 2 , 4 , 5 ]. The activation-loop or gatekeeper residues of FLT3 may be affected by these emergent mutations, although the acquisition of clones with additional mutations has been suggested as a cause of resistance in targeted therapy [ 6 ].…”

mentioning

confidence: 99%

Emergence of BCR-ABL1 (p190) in Acute Myeloid Leukemia Post-Gilteritinib Therapy

Kim

2023

Ann Lab Med

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Mechanisms of resistance to targeted therapies for relapsed or refractory acute myeloid leukemia

Cited by 7 publications

References 133 publications

Exploring the Molecular Landscape of Myelofibrosis, with a Focus on Ras and Mitogen-Activated Protein (MAP) Kinase Signaling

Exploring the Molecular Landscape of Myelofibrosis, with a Focus on Ras and Mitogen-Activated Protein (MAP) Kinase Signaling

Recent advance in phytonanomedicine and mineral nanomedicine delivery system of the treatment for acute myeloid leukemia

Emergence of BCR-ABL1 (p190) in Acute Myeloid Leukemia Post-Gilteritinib Therapy

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