Proteogenomic characterization of highly enriched viable leukemic blasts in acute myeloid leukemia: A SWOG report
Abstract Introduction Acute myeloid leukemia (AML) remains one of the deadliest hematopoietic malignancies. A better understanding of the molecular biology governing AML may lead to improved risk stratification and facilitate the development of novel therapies. Proteins are responsible for much of t...
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Wiley
2024-12-01
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| Online Access: | https://doi.org/10.1002/jha2.1041 |
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| author | Jasmine Naru Megan Othus ChenWei Lin Melinda A. Biernacki Marie Bleakley Thomas R. Chauncey Harry P. Erba Min Fang Matthew P. Fitzgibbon Phillip R. Gafken Richard G. Ivey Jacob J. Kennedy Travis D. Lorentzen Soheil Meshinchi Anna Moseley Era L. Pogosova‐Agadjanyan Vivian M. Liu Jerald P. Radich Uliana J. Voytovich Pei Wang Jeffrey R. Whiteaker Cheryl L. Willman Feinan Wu Amanda G. Paulovich Derek L. Stirewalt |
| author_facet | Jasmine Naru Megan Othus ChenWei Lin Melinda A. Biernacki Marie Bleakley Thomas R. Chauncey Harry P. Erba Min Fang Matthew P. Fitzgibbon Phillip R. Gafken Richard G. Ivey Jacob J. Kennedy Travis D. Lorentzen Soheil Meshinchi Anna Moseley Era L. Pogosova‐Agadjanyan Vivian M. Liu Jerald P. Radich Uliana J. Voytovich Pei Wang Jeffrey R. Whiteaker Cheryl L. Willman Feinan Wu Amanda G. Paulovich Derek L. Stirewalt |
| author_sort | Jasmine Naru |
| collection | DOAJ |
| description | Abstract Introduction Acute myeloid leukemia (AML) remains one of the deadliest hematopoietic malignancies. A better understanding of the molecular biology governing AML may lead to improved risk stratification and facilitate the development of novel therapies. Proteins are responsible for much of the biology of cells. Several studies have examined the global proteome in bulk mononuclear cells (MNCs) from AML specimens, which are comprised a heterogenous population of cells at various stages of differentiation. Methods Given the potential impact of the nonleukemic cells on protein expression profiles, we applied an integrative proteogenomic approach utilizing next‐generation sequencing and mass spectrometry‐based proteomics to identify novel protein biomarkers in unsorted MNCs and viable leukemic blasts (VLBs) isolated from blood and bone marrow specimens obtained at the time of AML diagnosis. Results We identified significant differences in protein expression between VLBs and MNCs. Subsequent studies (N = 27) focused on proteomic profiling of VLBs that identified novel candidate biomarkers associated with mutational genotypes and clinical outcome, some of which were recapitulated in an independent cohort of patients. Using mass spectrometry, we also detected mutated protein products, some of which were predicted via in silico analyses to be potential neoantigens amenable to adoptive immunotherapy. As previously described, analyses comparing transcript and protein expression showed an overall modest correlation between mRNA and protein dataset, but enriching for genes associated with mutations significantly improved the protein–RNA correlation. Conclusion Together, the results provide insight into the biology of VLBs and demonstrate the gains derived from examining the proteome in addition to genome and transcriptome. |
| format | Article |
| id | doaj-art-18d3b04e042e48a2a897b435a871a0b6 |
| institution | Kabale University |
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| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | eJHaem |
| spelling | doaj-art-18d3b04e042e48a2a897b435a871a0b62024-12-16T12:47:38ZengWileyeJHaem2688-61462024-12-01561243125110.1002/jha2.1041Proteogenomic characterization of highly enriched viable leukemic blasts in acute myeloid leukemia: A SWOG reportJasmine Naru0Megan Othus1ChenWei Lin2Melinda A. Biernacki3Marie Bleakley4Thomas R. Chauncey5Harry P. Erba6Min Fang7Matthew P. Fitzgibbon8Phillip R. Gafken9Richard G. Ivey10Jacob J. Kennedy11Travis D. Lorentzen12Soheil Meshinchi13Anna Moseley14Era L. Pogosova‐Agadjanyan15Vivian M. Liu16Jerald P. Radich17Uliana J. Voytovich18Pei Wang19Jeffrey R. Whiteaker20Cheryl L. Willman21Feinan Wu22Amanda G. Paulovich23Derek L. Stirewalt24Translational Science and Therapeutics Division Fred Hutch Seattle Washington USATranslational Science and Therapeutics Division Fred Hutch Seattle Washington USATranslational Science and Therapeutics Division Fred Hutch Seattle Washington USATranslational Science and Therapeutics Division Fred Hutch Seattle Washington USATranslational Science and Therapeutics Division Fred Hutch Seattle Washington USATranslational Science and Therapeutics Division Fred Hutch Seattle Washington USADuke Cancer Institute Durham North Carolina USATranslational Science and Therapeutics Division Fred Hutch Seattle Washington USAGenomics and Bioinformatics Shared Resource Fred Hutch Seattle Washington USAProteomics and Metabolomics Shared Resource Fred Hutch Seattle Washington USATranslational Science and Therapeutics Division Fred Hutch Seattle Washington USATranslational Science and Therapeutics Division Fred Hutch Seattle Washington USATranslational Science and Therapeutics Division Fred Hutch Seattle Washington USATranslational Science and Therapeutics Division Fred Hutch Seattle Washington USATranslational Science and Therapeutics Division Fred Hutch Seattle Washington USATranslational Science and Therapeutics Division Fred Hutch Seattle Washington USATranslational Science and Therapeutics Division Fred Hutch Seattle Washington USATranslational Science and Therapeutics Division Fred Hutch Seattle Washington USATranslational Science and Therapeutics Division Fred Hutch Seattle Washington USADepartment of Genetics and Genomics Icahn School of Medicine at Mount Sinai New York New York USATranslational Science and Therapeutics Division Fred Hutch Seattle Washington USADepartment of Laboratory Medicine and Pathology Mayo Clinic Comprehensive Cancer Center Rochester Minnesota USAGenomics and Bioinformatics Shared Resource Fred Hutch Seattle Washington USATranslational Science and Therapeutics Division Fred Hutch Seattle Washington USATranslational Science and Therapeutics Division Fred Hutch Seattle Washington USAAbstract Introduction Acute myeloid leukemia (AML) remains one of the deadliest hematopoietic malignancies. A better understanding of the molecular biology governing AML may lead to improved risk stratification and facilitate the development of novel therapies. Proteins are responsible for much of the biology of cells. Several studies have examined the global proteome in bulk mononuclear cells (MNCs) from AML specimens, which are comprised a heterogenous population of cells at various stages of differentiation. Methods Given the potential impact of the nonleukemic cells on protein expression profiles, we applied an integrative proteogenomic approach utilizing next‐generation sequencing and mass spectrometry‐based proteomics to identify novel protein biomarkers in unsorted MNCs and viable leukemic blasts (VLBs) isolated from blood and bone marrow specimens obtained at the time of AML diagnosis. Results We identified significant differences in protein expression between VLBs and MNCs. Subsequent studies (N = 27) focused on proteomic profiling of VLBs that identified novel candidate biomarkers associated with mutational genotypes and clinical outcome, some of which were recapitulated in an independent cohort of patients. Using mass spectrometry, we also detected mutated protein products, some of which were predicted via in silico analyses to be potential neoantigens amenable to adoptive immunotherapy. As previously described, analyses comparing transcript and protein expression showed an overall modest correlation between mRNA and protein dataset, but enriching for genes associated with mutations significantly improved the protein–RNA correlation. Conclusion Together, the results provide insight into the biology of VLBs and demonstrate the gains derived from examining the proteome in addition to genome and transcriptome.https://doi.org/10.1002/jha2.1041AMLhematological malignancyneoantigensproteogenomicstranscriptomics |
| spellingShingle | Jasmine Naru Megan Othus ChenWei Lin Melinda A. Biernacki Marie Bleakley Thomas R. Chauncey Harry P. Erba Min Fang Matthew P. Fitzgibbon Phillip R. Gafken Richard G. Ivey Jacob J. Kennedy Travis D. Lorentzen Soheil Meshinchi Anna Moseley Era L. Pogosova‐Agadjanyan Vivian M. Liu Jerald P. Radich Uliana J. Voytovich Pei Wang Jeffrey R. Whiteaker Cheryl L. Willman Feinan Wu Amanda G. Paulovich Derek L. Stirewalt Proteogenomic characterization of highly enriched viable leukemic blasts in acute myeloid leukemia: A SWOG report eJHaem AML hematological malignancy neoantigens proteogenomics transcriptomics |
| title | Proteogenomic characterization of highly enriched viable leukemic blasts in acute myeloid leukemia: A SWOG report |
| title_full | Proteogenomic characterization of highly enriched viable leukemic blasts in acute myeloid leukemia: A SWOG report |
| title_fullStr | Proteogenomic characterization of highly enriched viable leukemic blasts in acute myeloid leukemia: A SWOG report |
| title_full_unstemmed | Proteogenomic characterization of highly enriched viable leukemic blasts in acute myeloid leukemia: A SWOG report |
| title_short | Proteogenomic characterization of highly enriched viable leukemic blasts in acute myeloid leukemia: A SWOG report |
| title_sort | proteogenomic characterization of highly enriched viable leukemic blasts in acute myeloid leukemia a swog report |
| topic | AML hematological malignancy neoantigens proteogenomics transcriptomics |
| url | https://doi.org/10.1002/jha2.1041 |
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