Immunophenotypic and Molecular Features of Acute Myeloid Leukemia with Plasmacytoid Dendritic Cell Differentiation Are Distinct from Blastic Plasmacytoid Dendritic Cell Neoplasm
Acute myeloid leukemia (AML) with ≥2% plasmacytoid dendritic cells (pDC) has been recently described as AML with pDC differentiation (pDC-AML) characterized by pDC expansion with frequent <i>RUNX1</i> mutations. In this study, we investigated a cohort of 53 pDC-AML cases representing abo...
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MDPI AG
2022-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/14/3375 |
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| author | Wei Wang Jie Xu Joseph D. Khoury Naveen Pemmaraju Hong Fang Roberto N. Miranda C. Cameron Yin Siba El Hussein Fuli Jia Zhenya Tang Shimin Hu Marina Konopleva L. Jeffrey Medeiros Sa A. Wang |
| author_facet | Wei Wang Jie Xu Joseph D. Khoury Naveen Pemmaraju Hong Fang Roberto N. Miranda C. Cameron Yin Siba El Hussein Fuli Jia Zhenya Tang Shimin Hu Marina Konopleva L. Jeffrey Medeiros Sa A. Wang |
| author_sort | Wei Wang |
| collection | DOAJ |
| description | Acute myeloid leukemia (AML) with ≥2% plasmacytoid dendritic cells (pDC) has been recently described as AML with pDC differentiation (pDC-AML) characterized by pDC expansion with frequent <i>RUNX1</i> mutations. In this study, we investigated a cohort of 53 pDC-AML cases representing about 3% of all AML cases. We characterized their immunophenotype and genetic profiles and compared these findings with blastic plasmacytoid dendritic cell neoplasm (BPDCN). pDC-differentiation/expansion was preferentially observed in AML with an immature myeloid or myelomonocytic immunophenotype, where myeloblasts were frequently positive for CD34 (98%), CD117 (94%), HLA-DR (100%) and TdT (79%), with increased CD123 (89%) expression. The median number of pDCs in pDC-AML was 6.6% (range, 2% to 26.3%) and their immunophenotype reminiscent of pDCs in early or intermediate stages of differentiation. The immunophenotype of pDCs in pDC-AML was different from BPDCN (<i>n</i> = 39), with major disparities in CD34 (96% vs. 0%), CD56 (8% vs. 97%) and TCL1 (12% vs. 98%) and significant differences in frequency of CD4, CD13, CD22, CD25, CD36, CD38, CD117 and CD303 expression. At the molecular level, the genetic landscapes of pDC-AML and BPDCN also differ, with <i>RUNX1</i> mutations detected in 64% of pDC-AML versus 2% of BPDCN. Disparities in <i>TET2</i> (21% vs. 56%), <i>FLT3</i> (23% vs. 0%), <i>DNMT3A</i> (32% vs. 10%) and <i>ZRSR2</i> (2% vs. 16%) (all <i>p</i> < 0.05) were also detected. The distinct immunophenotypic and mutation profiles of pDC-AML and BPDCN indicate that the neoplastic pDCs in pDC-AML and BPDCN derived from different subsets of pDC precursors. |
| first_indexed | 2024-03-09T12:07:42Z |
| format | Article |
| id | doaj.art-76b5125e070b496392700ad9546198a3 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T12:07:42Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-76b5125e070b496392700ad9546198a32023-11-30T22:56:08ZengMDPI AGCancers2072-66942022-07-011414337510.3390/cancers14143375Immunophenotypic and Molecular Features of Acute Myeloid Leukemia with Plasmacytoid Dendritic Cell Differentiation Are Distinct from Blastic Plasmacytoid Dendritic Cell NeoplasmWei Wang0Jie Xu1Joseph D. Khoury2Naveen Pemmaraju3Hong Fang4Roberto N. Miranda5C. Cameron Yin6Siba El Hussein7Fuli Jia8Zhenya Tang9Shimin Hu10Marina Konopleva11L. Jeffrey Medeiros12Sa A. Wang13Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAAcute myeloid leukemia (AML) with ≥2% plasmacytoid dendritic cells (pDC) has been recently described as AML with pDC differentiation (pDC-AML) characterized by pDC expansion with frequent <i>RUNX1</i> mutations. In this study, we investigated a cohort of 53 pDC-AML cases representing about 3% of all AML cases. We characterized their immunophenotype and genetic profiles and compared these findings with blastic plasmacytoid dendritic cell neoplasm (BPDCN). pDC-differentiation/expansion was preferentially observed in AML with an immature myeloid or myelomonocytic immunophenotype, where myeloblasts were frequently positive for CD34 (98%), CD117 (94%), HLA-DR (100%) and TdT (79%), with increased CD123 (89%) expression. The median number of pDCs in pDC-AML was 6.6% (range, 2% to 26.3%) and their immunophenotype reminiscent of pDCs in early or intermediate stages of differentiation. The immunophenotype of pDCs in pDC-AML was different from BPDCN (<i>n</i> = 39), with major disparities in CD34 (96% vs. 0%), CD56 (8% vs. 97%) and TCL1 (12% vs. 98%) and significant differences in frequency of CD4, CD13, CD22, CD25, CD36, CD38, CD117 and CD303 expression. At the molecular level, the genetic landscapes of pDC-AML and BPDCN also differ, with <i>RUNX1</i> mutations detected in 64% of pDC-AML versus 2% of BPDCN. Disparities in <i>TET2</i> (21% vs. 56%), <i>FLT3</i> (23% vs. 0%), <i>DNMT3A</i> (32% vs. 10%) and <i>ZRSR2</i> (2% vs. 16%) (all <i>p</i> < 0.05) were also detected. The distinct immunophenotypic and mutation profiles of pDC-AML and BPDCN indicate that the neoplastic pDCs in pDC-AML and BPDCN derived from different subsets of pDC precursors.https://www.mdpi.com/2072-6694/14/14/3375acute myeloid leukemiaBPDCNplasmacytoid dendritic cellsimmunophenotypeflow cytometrymutation |
| spellingShingle | Wei Wang Jie Xu Joseph D. Khoury Naveen Pemmaraju Hong Fang Roberto N. Miranda C. Cameron Yin Siba El Hussein Fuli Jia Zhenya Tang Shimin Hu Marina Konopleva L. Jeffrey Medeiros Sa A. Wang Immunophenotypic and Molecular Features of Acute Myeloid Leukemia with Plasmacytoid Dendritic Cell Differentiation Are Distinct from Blastic Plasmacytoid Dendritic Cell Neoplasm Cancers acute myeloid leukemia BPDCN plasmacytoid dendritic cells immunophenotype flow cytometry mutation |
| title | Immunophenotypic and Molecular Features of Acute Myeloid Leukemia with Plasmacytoid Dendritic Cell Differentiation Are Distinct from Blastic Plasmacytoid Dendritic Cell Neoplasm |
| title_full | Immunophenotypic and Molecular Features of Acute Myeloid Leukemia with Plasmacytoid Dendritic Cell Differentiation Are Distinct from Blastic Plasmacytoid Dendritic Cell Neoplasm |
| title_fullStr | Immunophenotypic and Molecular Features of Acute Myeloid Leukemia with Plasmacytoid Dendritic Cell Differentiation Are Distinct from Blastic Plasmacytoid Dendritic Cell Neoplasm |
| title_full_unstemmed | Immunophenotypic and Molecular Features of Acute Myeloid Leukemia with Plasmacytoid Dendritic Cell Differentiation Are Distinct from Blastic Plasmacytoid Dendritic Cell Neoplasm |
| title_short | Immunophenotypic and Molecular Features of Acute Myeloid Leukemia with Plasmacytoid Dendritic Cell Differentiation Are Distinct from Blastic Plasmacytoid Dendritic Cell Neoplasm |
| title_sort | immunophenotypic and molecular features of acute myeloid leukemia with plasmacytoid dendritic cell differentiation are distinct from blastic plasmacytoid dendritic cell neoplasm |
| topic | acute myeloid leukemia BPDCN plasmacytoid dendritic cells immunophenotype flow cytometry mutation |
| url | https://www.mdpi.com/2072-6694/14/14/3375 |
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