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Ugeskrift For Laeger Oct 2021Myeloid neoplasms with germ line predisposition (hMN) are likely underdiagnosed and are estimated to constitute a substantial fraction of patients with myelodysplastic... (Review)
Review
Myeloid neoplasms with germ line predisposition (hMN) are likely underdiagnosed and are estimated to constitute a substantial fraction of patients with myelodysplastic syndrome and acute myeloid leukaemia. Correct diagnosis of hMN is vital, as it can influence treatment decisions, facilitate genetic counselling and help identify family members at risk. In this review, we describe the symptoms associated with hMN and present an example of the underlying molecular mechanism. Furthermore, we summarise the current knowledge and recommendations for diagnosis, surveillance and treatment of hMN.
Topics: Adult; Genetic Predisposition to Disease; Germ Cells; Germ-Line Mutation; Humans; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
PubMed: 34709158
DOI: No ID Found -
Journal of Cellular and Molecular... Feb 2021Wnt-Fzd signalling pathway plays a critical role in acute myeloid leukaemia (AML) progression and oncogenicity. There is no study to investigate the prognostic value of...
Wnt-Fzd signalling pathway plays a critical role in acute myeloid leukaemia (AML) progression and oncogenicity. There is no study to investigate the prognostic value of Wnt and Fzd gene families in AML. Our study screened 84 AML patients receiving chemotherapy only and 71 also undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT) from the Cancer Genome Atlas (TCGA) database. We found that some Wnt and Fzd genes had significant positive correlations. The expression levels of Fzd gene family were independent of survival in AML patients. In the chemotherapy group, AML patients with high Wnt2B or Wnt11 expression had significantly shorter event-free survival (EFS) and overall survival (OS); high Wnt10A expressers had significantly longer OS than the low expressers (all P < .05), whereas, in the allo-HSCT group, the expression levels of Wnt gene family were independent of survival. We further found that high expression of Wnt10A and Wnt11 had independent prognostic value, and the patients with high Wnt10A and low Wnt11 expression had the longest EFS and OS in the chemotherapy group. Pathway enrichment analysis showed that genes related to Wnt10A, Wnt11 and Wnt 2B were mainly enriched in 'cell morphogenesis involved in differentiation', 'haematopoietic cell lineage', 'platelet activation, signalling and aggregation' and 'mitochondrial RNA metabolic process' signalling pathways. Our results indicate that high Wnt2B and Wnt11 expression predict poor prognosis, and high Wnt10A expression predicts favourable prognosis in AML, but their prognostic effects could be neutralized by allo-HSCT. Combined Wnt10A and Wnt11 may be a novel prognostic marker in AML.
Topics: Adult; Aged; Biomarkers, Tumor; Databases, Genetic; Female; Frizzled Receptors; Gene Expression Regulation, Leukemic; Humans; Kaplan-Meier Estimate; Leukemia, Myeloid, Acute; Male; Middle Aged; Multigene Family; Neoplasm Grading; Neoplasm Staging; Prognosis; Wnt Proteins
PubMed: 33417298
DOI: 10.1111/jcmm.16233 -
British Journal of Pharmacology Jul 2022Targeting cancer metabolism has emerged as an attractive approach to improve therapeutic regimens in acute myeloid leukaemia (AML). Mitochondrial proteases are closely... (Review)
Review
Targeting cancer metabolism has emerged as an attractive approach to improve therapeutic regimens in acute myeloid leukaemia (AML). Mitochondrial proteases are closely related to cancer metabolism, but their biological functions have not been well characterized in AML. According to different categories, we comprehensively review the role of mitochondrial proteases in AML. This review highlights some 'powerful' mitochondrial protease targets, including their biological function, chemical modulators, and applicative prospect in AML.
Topics: Humans; Leukemia, Myeloid, Acute; Mitochondria; Peptide Hydrolases
PubMed: 35352341
DOI: 10.1111/bph.15844 -
Clinical and Translational Medicine Jun 2023Genetic mutations of IKZF1 have been frequently delineated in B-lineage acute leukaemia (B-ALL) but rarely elucidated in acute myeloid leukaemia (AML). IKZF1 mutations...
BACKGROUND
Genetic mutations of IKZF1 have been frequently delineated in B-lineage acute leukaemia (B-ALL) but rarely elucidated in acute myeloid leukaemia (AML). IKZF1 mutations confer a poor prognosis in AML, and hotspot mutations of IKZF1, N159Y and N159S tend to occur in B-ALL and AML respectively. However, the pathogenesis of IKZF1 N159S in AML and IKZF1 lineage susceptibility are largely unknown.
METHODS
The genetic and clinical characteristics of IKZF1-mutated AML patients were evaluated. Multi-omics analysis and functional assays were performed in vitro using IKZF1 mutations knock-in AML cell lines.
RESULTS
23 (4.84%) small sequence variants of IKZF1 were identified in 475 newly diagnosed AML (non-M3) patients. Based on RNA sequencing, three classes of IKZF1-related AML were defined, including 9 patients (39.13%) with IKZF1 N159S mutations, 10 (43.47%) with CEBPA mutations and 4 others (17.39%). IKZF1 N159S may define a unique subgroup with higher HOXA/B expression and native B-cell immune fractions. Gene expression data of multiple knock-in cell lines indicate that the lymphocyte differentiation-related MME and CD44 kept high expression in IKZF1 N159Y but were downregulated in N159S. CUT&TAG sequencing showed that IKZF1 N159S reshaped the binding profiles of IKZF1. Integration analysis suggested that the pathogenesis of IKZF1 N159S may depend on the deregulation of several cofactors, such as oncogenic MYC and CPNE7 targets.
CONCLUSIONS
Collectively, we dissected the molecular spectrum and clinical features of IKZF1-related AML, which may promote an in-depth understanding of the pathogenesis, lineage susceptibility and clinical research of AML.
Topics: Leukemia, Myeloid, Acute; Humans; Ikaros Transcription Factor; Mutation; Transcriptome; Proto-Oncogene Proteins c-myc; Membrane Proteins
PubMed: 37345307
DOI: 10.1002/ctm2.1309 -
Cancer Immunology, Immunotherapy : CII Jul 2007The treatment of myeloid leukaemia has progressed in recent years with the advent of donor leukocyte infusions (DLI), haemopoietic stem cell transplants (HSCTs) and... (Review)
Review
The treatment of myeloid leukaemia has progressed in recent years with the advent of donor leukocyte infusions (DLI), haemopoietic stem cell transplants (HSCTs) and targeted therapies. However, relapse has a high associated morbidity rate and a method for removing diseased cells in first remission, when a minimal residual disease state is achieved and tumour load is low, has the potential to extend remission times and prevent relapse especially when used in combination with conventional treatments. Acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) are heterogeneous diseases which lack one common molecular target while chronic myeloid leukaemia (CML) patients have experienced prolonged remissions through the use of targeted therapies which remove BCR-ABL(+) cells effectively in early chronic phase. However, escape mutants have arisen and this therapy has little effectivity in the late chronic phase. Here we review the immune therapies which are close to or in clinical trials for the myeloid leukaemias and describe their potential advantages and disadvantages.
Topics: Clinical Trials as Topic; Humans; Immunotherapy; Leukemia, Myeloid
PubMed: 17180671
DOI: 10.1007/s00262-006-0267-y -
British Journal of Haematology Aug 2015
Topics: Female; Humans; Leukemia, Myeloid, Acute; Pregnancy; Pregnancy Complications, Neoplastic
PubMed: 26104019
DOI: 10.1111/bjh.13550 -
Clinical and Experimental Immunology Aug 2010While chemotherapy is successful at inducing remission of acute myeloid leukaemia (AML), the disease has a high probability of relapse. Strategies to prevent relapse... (Review)
Review
While chemotherapy is successful at inducing remission of acute myeloid leukaemia (AML), the disease has a high probability of relapse. Strategies to prevent relapse involve consolidation chemotherapy, stem cell transplantation and immunotherapy. Evidence for immunosurveillance of AML and susceptibility of leukaemia cells to both T cell and natural killer (NK) cell attack and justifies the application of immune strategies to control residual AML persisting after remission induction. Immune therapy for AML includes allogeneic stem cell transplantation, adoptive transfer of allogeneic or autologous T cells or NK cells, vaccination with leukaemia cells, dendritic cells, cell lysates, peptides and DNA vaccines and treatment with cytokines, antibodies and immunomodulatory agents. Here we describe what is known about the immunological features of AML at presentation and in remission, the current status of immunotherapy and strategies combining treatment approaches with a view to achieving leukaemia cure.
Topics: Animals; Humans; Immunotherapy; Leukemia, Myeloid, Acute
PubMed: 20529084
DOI: 10.1111/j.1365-2249.2010.04197.x -
Ear, Nose, & Throat Journal Sep 2016Myeloid sarcoma is a rare extramedullary tumor composed of malignant myeloid cells that occur in the presence of myeloid leukemia. We report a case series of pediatric...
Myeloid sarcoma is a rare extramedullary tumor composed of malignant myeloid cells that occur in the presence of myeloid leukemia. We report a case series of pediatric head and neck myeloid sarcomas representative of the epidemiology, symptomatology, laboratorial correlations, prognoses, and treatment of extramedullary leukemia. Presented are 3 cases involving patients ranging from 17 months to 11 years of age. Two patients were successfully treated with chemotherapy, and in the third patient, a large lytic lesion was treated palliatively with proton beam therapy. Knowledge and recognition of myeloid sarcomas is important as they can be locally invasive, and they may also be used as a diagnostic tool or a prognostic indicator for leukemia.
Topics: Child; Child, Preschool; Fatal Outcome; Female; Head and Neck Neoplasms; Humans; Infant; Leukemia, Myeloid; Male; Sarcoma, Myeloid
PubMed: 27657319
DOI: 10.1177/014556131609500902 -
British Journal of Haematology Oct 2005Children with Down syndrome (DS) are at increased risk of leukaemia. Myeloid disorders include transient abnormal myelopoiesis (TAM), myelodysplasia (MDS) and acute... (Review)
Review
Children with Down syndrome (DS) are at increased risk of leukaemia. Myeloid disorders include transient abnormal myelopoiesis (TAM), myelodysplasia (MDS) and acute myeloid leukaemia (AML). Mutations in the GATA-1 gene, which encodes for a transcription factor central to the normal development of the erythroid and megakaryocytic lineages, are found in cases of TAM, MDS and AML in DS children. DS children with MDS/AML mostly present between the ages of 1 and 4 years, and have a large predominance of megakaryoblastic disease (French-American-British type M7). The MDS and AML are part of a single disease entity (myeloid leukaemia of Down syndrome) that is extremely sensitive to chemotherapy. Resistant disease and relapse are rare, but treatment-related toxicity is high, and deaths in remission have exceeded those due to disease in most series. Accordingly, controlled dosage reduction is the focus of contemporary treatment studies.
Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Down Syndrome; Drug Administration Schedule; Humans; Infant; Leukemia, Myeloid; Megakaryocytes; Neural Tube Defects
PubMed: 16173956
DOI: 10.1111/j.1365-2141.2005.05700.x -
British Journal of Haematology Mar 2018
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Neoplasms; Eye Neoplasms; Female; Humans; Leukemia, Myeloid; Magnetic Resonance Imaging; Male; Middle Aged; Young Adult
PubMed: 27879987
DOI: 10.1111/bjh.14430