MYC protein expression does not correlate with MYC abnormalities detected by FISH but predicts an unfavorable prognosis in de novo acute myeloid leukemia

Chen, Pu; Redd, Lucas; Schmidt, Yao; Koduru, Prasad; Fuda, Franklin; Montgomery-Goecker, Crystal; Kumar, K. Shiva; Xu-Monette, Zijun Y.; Young, Ken H.; Collins, Robert H.; Chen, Weina

doi:10.1016/j.leukres.2021.106584

Cited by 5 publications

(6 citation statements)

References 28 publications

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“…Studies on haematological malignancies have previously demonstrated that MYC activation can be caused by FLT3 ‐ITD mutation 21 . Therefore, we hypothesised that there might be an upstream‐downstream relationship between BCAT1 and MYC .…”

Section: Resultsmentioning

confidence: 98%

“…Studies on haematological malignancies have previously demonstrated that MYC activation can be caused by FLT3-ITD mutation. 21 Therefore, we hypothesised that there might be an upstream-downstream relationship between BCAT1 and MYC. To verify this hypothesis, we extracted the expression data of BCAT1 and MYC from TCGA-AML and Beat-AML databases and analysed their correlation.…”

Section: The Flt3-itd/bcat1/myc Signalling Pathway Plays a Biological...mentioning

confidence: 99%

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Prognostic impact of FLT3‐ITD mutation on NPM1⁺ acute myeloid leukaemia patients and related molecular mechanisms

Pan,

Chang,

Ruan

et al. 2023

Br J Haematol

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SummaryThe prognosis of acute myeloid leukaemia (AML) patients carrying NPM1 mutations is significantly worse when accompanied by FLT3‐ITD mutations. However, accurate quantitative detection of FLT3‐ITD mutations remains challenging. To identify a novel biomarker in NPM1+FLT3‐ITD+ AML patients for more accurate stratification, we analysed the differential gene expression between the NPM1+FLT3‐ITD+ and NPM1+FLT3‐ITD− groups in five public AML datasets and identified a biomarker by taking the intersection of differentially expressed genes. We validated this biomarker in bone marrow samples from NPM1+ AML patients at the Peking University Institute of Haematology and analysed its prognostic significance. BCAT1 expression was higher in the NPM1+FLT3‐ITD+ group than in the NPM1+FLT3‐ITD− group in all seven cohorts. BCAT1 was able to predict the prognosis of NPM1+FLT3‐ITD+ AML patients, and its predictive ability was superior to that of the FLT3‐ITD allelic ratio (AR). FLT3‐targeted inhibitor quizartinib reduced BCAT1 expression. BCAT1 knockdown using lentiviral vectors led to the downregulation of MYC expression. Thus, we identified BCAT1 as a novel biomarker for NPM1+FLT3‐ITD+ AML patients. The FLT3‐ITD/BCAT1/MYC signalling pathway may play a biological role in promoting the occurrence and development of AML in FLT3‐ITD+ cell lines.

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Section: Resultsmentioning

confidence: 98%

Section: The Flt3-itd/bcat1/myc Signalling Pathway Plays a Biological...mentioning

confidence: 99%

Prognostic impact of FLT3‐ITD mutation on NPM1⁺ acute myeloid leukaemia patients and related molecular mechanisms

Pan,

Chang,

Ruan

et al. 2023

Br J Haematol

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“…All eligible patients were treated with a standardized chemotherapy protocol. Common regimens included hyper‐CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) and 7 + 3 (7 days of cytarabine + 3 days of idarubicin) for other MPAL subtype patients, hyper‐CVAD and CALGB 10403 (vincristine, PEG‐asparaginase, prednisone, and daunorubicin) for B/myeloid MPAL isoMPO and B‐ALL pateints, 10 and 7 + 3 for AML patients 11 . Common clinical therapy regimens for WHO 2008 MPAL included those for other MPAL subtypes or B/myeloid MPAL isoMPO patients.…”

Section: Resultsmentioning

confidence: 99%

“…Clinical and laboratory data were obtained by review of electronic medical records among various leukemias, including WHO 2008 MPAL, B/myeloid MPAL isoMPO , other MPAL subtypes, and previously reported cohorts of de novo adult B-ALL (n = 64, median age 42 years, range 18-76 years, 41 males and 23 females; part of the results published 10 ) and de novo adult AML (n = 58, median age 53 years, range 19-80 years, 30 males and 28 females). 11 The study was approved by the Institutional Review Board at the University of Texas Southwestern Medical Center and carried out in accordance with the Declaration of Helsinki. Part of this study was presented at the 2016 United States Canadian Annual Pathology Meeting.…”

Section: Case Identificationmentioning

confidence: 99%

“…All cases (peripheral blood or bone marrow aspirate samples) were routinely processed, and immunophenotyped using 4-color FACSCalibur flow cytometer (Becton Dickinson, San Jose, CA, USA), and analyzed by cluster analysis using CytoPaint Classic (Leukobyte, Pleasanton, CA, USA), as previously described. 11,13 The four-color antibody combinations/tubes [fluorescein isothiocyanate (FITC)/phycoerythrin (PE)/peridinin chlorophyll protein (PerCP)/allophycocyanin (APC)] were as follows: CD10/CD22/CD20/CD34, CD34/CD14/CD45/CD38, pλ/pΚ/ CD20/CD19, CD36/CD63/CD45/CD34, CD16/CD56/CD45/CD11b, CD15/CD33/CD45/CD34, CD2/CD117/CD45/CD34, CD34/CD13/ HLA-DR/CD19, intracellular MPO/CD79a/CD45/CD34, and intracellular TdT/CD22/CD3/CD45. A total of 30 000 events/tube was collected.…”

Section: Flow Cytometrymentioning

confidence: 99%

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Adult mixed phenotype acute leukemia (MPAL): B/myeloid MPAL^isoMPO is distinct from other MPAL subtypes

Weinberg

Dennis

Zia

et al. 2022

Int J Lab Hematology

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Introduction: Myeloperoxidase (MPO) is considered a specific marker of myeloid/ non-monocytic lineage in the diagnosis of mixed phenotype acute leukemia (MPAL). However, the clinical significance of isolated dim MPO expression in otherwise typical B lymphoblastic leukemia (B-ALL; referred to as B/myeloid MPAL isoMPO ) in adult patients is unknown. Methods: We compared flow cytometric immunophenotype and clinicopathological findings among cases of B/myeloid MPAL isoMPO (n = 13), other MPAL subtypes (n = 10, B/myeloid and T/myeloid MPAL), B-ALL (n = 64), and acute myeloid leukemia (AML, n = 58), using the 2016 WHO classification. For MPAL cases, MPO was reported as the percent of MPO positive blasts and its intensity (dim or moderate/ strong). The pattern of heterogenous antigen expression (inversely coordinated expression between myeloid and lymphoid markers and cell size) was assessed. Results: Cases of B/myeloid MPAL isoMPO showed a fairly homogenous single Blineage blast population with dim MPO expression whereas cases of other MPAL subtypes displayed heterogeneous antigen expression and moderate/strong MPO expression. The percent of MPO positive blasts in these two groups was similar. Expressions of CD15, CD117, and monocytic markers were more common in other MPAL than in B/myeloid MPAL isoMPO . B/myeloid MPAL isoMPO patients had similar overall and leukemia free survivals as B-ALL patients and better than other MPAL patients. Conclusion: This is the first study to investigate the clinical significance of adult B/myeloid MPAL isoMPO using the 2016 WHO classification. Our results suggest that B/myeloid MPAL isoMPO clinically behaves more similarly to B-ALL than to other MPAL subtypes, supporting the 2016 WHO classification to segregate this entity from other MPAL subtypes.

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Distinct mutational and clinicopathologic profiles characterize acute myeloid leukemia with cup-like nuclei

et al. 2023

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MYC protein expression does not correlate with MYC abnormalities detected by FISH but predicts an unfavorable prognosis in de novo acute myeloid leukemia

Cited by 5 publications

References 28 publications

Prognostic impact of FLT3‐ITD mutation on NPM1⁺ acute myeloid leukaemia patients and related molecular mechanisms

Prognostic impact of FLT3‐ITD mutation on NPM1⁺ acute myeloid leukaemia patients and related molecular mechanisms

Adult mixed phenotype acute leukemia (MPAL): B/myeloid MPAL^isoMPO is distinct from other MPAL subtypes

Distinct mutational and clinicopathologic profiles characterize acute myeloid leukemia with cup-like nuclei

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MYC protein expression does not correlate with MYC abnormalities detected by FISH but predicts an unfavorable prognosis in de novo acute myeloid leukemia

Cited by 5 publications

References 28 publications

Prognostic impact of FLT3‐ITD mutation on NPM1+ acute myeloid leukaemia patients and related molecular mechanisms

Prognostic impact of FLT3‐ITD mutation on NPM1+ acute myeloid leukaemia patients and related molecular mechanisms

Adult mixed phenotype acute leukemia (MPAL): B/myeloid MPALisoMPO is distinct from other MPAL subtypes

Distinct mutational and clinicopathologic profiles characterize acute myeloid leukemia with cup-like nuclei

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Prognostic impact of FLT3‐ITD mutation on NPM1⁺ acute myeloid leukaemia patients and related molecular mechanisms

Prognostic impact of FLT3‐ITD mutation on NPM1⁺ acute myeloid leukaemia patients and related molecular mechanisms

Adult mixed phenotype acute leukemia (MPAL): B/myeloid MPAL^isoMPO is distinct from other MPAL subtypes