Targeting and Monitoring Acute Myeloid Leukaemia with Nucleophosmin-1 (NPM1) Mutation

Chin, Lynn; Wong, Chantelle Ye Gwen; Gill, Harinder

doi:10.3390/ijms24043161

Cited by 10 publications

(9 citation statements)

References 166 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Patients with CMML carrying the NPM1 mutation presented at a relatively young age, with a median of 60 years (range, . This subgroup exhibited distinctive characteristics, including a median bone marrow blast count of 13% (10)(11)(12)(13)(14)(15)(16)(17)(18)(19), leukocytes of 15.7 × 10 9 (12.24-30.6), a platelet count of 98 × 10 9 (35-110), and a median hemoglobin concentration of 85 g/L (49-138). Among these five patients, three were eligible for intensive chemotherapy and attained a complete response with a significant reduction in NPM1 ratio.…”

Section: Seven Additional Cases Of Unusual Presentation Of Npm1mut Mnmentioning

confidence: 99%

“…Finally, various NPM1-targeted approaches such as menin inhibitors and FLT3 kinase inhibitors are under investigation with promising results [10,33], which warrants the identification of this potential druggable candidate in all patients with a myeloid malignancy [16].…”

Section: Review 41 Npm1 In Leukemogenesis and Its Clinical Impactmentioning

confidence: 99%

“…Conversely, they suggest that older unfit patients with unfavorable genetic risk (complex karyotype, rearranged MECOM, TP53 mutations) should be treated with hypomethylating agents in combination with novel and promising agents such as venetoclax [14]. As the understanding of NPM1 mutations and their consequences has recently become clearer, various targeting approaches such as menin inhibitors are under investigation [16], particularly for refractory and relapsed AML patients.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Infrequent Presentations of Chronic NPM1-Mutated Myeloid Neoplasms: Clinicopathological Features of Eight Cases from a Single Institution and Review of the Literature

Castaño-Díez,

Guijarro,

López-Guerra

et al. 2024

Cancers

View full text Add to dashboard Cite

Non-acute myeloid neoplasms (MNs) with NPM1 mutations (NPM1mut-MNs) pose a diagnostic and therapeutic dilemma, primarily manifesting as chronic myelomonocytic leukemia (CMML) and myelodysplastic syndromes (MDS). The classification and treatment approach for these conditions as acute myeloid leukemia (AML) are debated. We describe eight cases of atypical NPM1mut-MNs from our institution and review the literature. We include a rare case of concurrent prostate carcinoma and MN consistent with chronic eosinophilic leukemia, progressing to myeloid sarcoma of the skin. Of the remaining seven cases, five were CMML and two were MDS. NPM1 mutations occur in 3–5% of CMML and 1–6% of MDS, with an increased likelihood of rapid evolution to AML. Their influence on disease progression varies, and their prognostic significance in non-acute MNs is less established than in AML. Non-acute MNs with NPM1 mutations may display an aggressive clinical course, emphasizing the need for a comprehensive diagnosis integrating clinical and biological data. Tailoring patient management on an individualized basis, favoring intensive treatment aligned with AML protocols, is crucial, regardless of blast percentage. Research on the impact of NPM1 mutations in non-acute myeloid neoplasms is ongoing, requiring challenging prospective studies with substantial patient cohorts and extended follow-up periods for validation.

show abstract

Section: Seven Additional Cases Of Unusual Presentation Of Npm1mut Mnmentioning

confidence: 99%

Section: Review 41 Npm1 In Leukemogenesis and Its Clinical Impactmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Infrequent Presentations of Chronic NPM1-Mutated Myeloid Neoplasms: Clinicopathological Features of Eight Cases from a Single Institution and Review of the Literature

Castaño-Díez,

Guijarro,

López-Guerra

et al. 2024

Cancers

View full text Add to dashboard Cite

show abstract

“…We have shown that these combinations can increase antigenspecific immune responses against leukemic cells as well as LPC/LSC [82,83]. Image generated using information from the following articles [5][6][7][8]27,39,41,47,55,56,[64][65][66][67][68][69][70][71]80,[83][84][85][86][87][88].…”

Section: Figure 2 Combinations Of Immunotherapeutic Treatments Can Us...mentioning

confidence: 99%

Immunotherapeutic Potential of Mutated NPM1 for the Treatment of AML

Greiner,

Mohamed,

Fletcher

et al. 2024

Preprint

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is a malignant disease of the blood and bone marrow that is characterized by uncontrolled clonal proliferation of abnormal myeloid progenitor cells. Nucleophosmin 1 (NPM1) gene mutations are the most common genetic abnormality in AML, detectable in blast cells from about one third of adults with AML. AML NPM1mut is recognized as a separate entity in the World Health Organization (WHO) classification of AML. Clinical and survival data suggest that patients with this form of AML often have a more favorable prognosis, which may be due to the immunogenicity created by the mutations in the NPM1 protein. Consequently, AML with NPM1mut can be considered an immunogenic subtype of AML. However, the underlying mechanisms of this immunogenicity and associated favorable survival outcomes need to be further investigated. Immune checkpoint molecules, such as the programmed cell death-1 (PD-1) protein and its ligand, PD-L1, play important roles in leukemogenesis through their maintenance of an immunosuppressive tumor microenvironment. Preclinical trials have shown that the use of PD-1/PD-L1 (PDx) checkpoint inhibitors in solid tumors and lymphoma work best in novel therapy combinations. Patients with NPM1mut AML may be better suited to immunogenic strategies that are based on the inhibition of the immune checkpoint pathway of PDx than patients without this mutation, suggesting the genetic landscape of patients may also inform best practice for the use of PDx inhibitors.

show abstract

“…The potential of VISTA blockade as an immunotherapeutic strategy against AML with the aim of boosting antitumor immune responses and modulating the inflammatory microenvironment is discussed. Furthermore, our contributing authors provide comprehensive reviews concerning the impact of mutations or dysregulation of key proteins such as TET proteins [ 5 ], IKAROS [ 6 ], S100A8/9 [ 7 ], NPM1 [ 8 ], and RasGRP [ 9 ] on hematologic malignancies, along with potential therapeutic strategies targeting these molecules for diagnosis and treatment. Another review addresses metabolic reprogramming in lymphomas, exploring potential signaling pathways driving these alterations and discussing therapeutic strategies targeting metabolic pathways [ 10 ].…”

mentioning

confidence: 99%