Plasmacytoid dendritic cells proliferation associated with acute myeloid leukemia: phenotype profile and mutation landscape
(1)
,
(2)
,
(3)
,
(4)
,
(3)
,
(3)
,
(5)
,
(6)
,
(3)
,
(4)
,
(6)
,
(6)
,
(7)
,
(7)
,
(8)
,
(9)
,
(10)
,
(11)
,
(12)
,
(13)
,
(14)
,
(15)
,
(16)
,
(17)
,
(17)
,
(18)
,
(19)
,
(20, 21)
,
(22)
,
(23)
,
(4)
,
(3)
,
(3)
,
(3)
,
(4)
,
(2)
,
(3)
,
(3)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
Meyling Cheok
- Function : Author
- PersonId : 769023
- ORCID : 0000-0002-7820-8026
- IdRef : 19092876X
Eric Deconinck
- Function : Author
- PersonId : 759821
- ORCID : 0000-0002-6006-8088
Damien Roos-Weil
- Function : Author
- PersonId : 791867
- ORCID : 0000-0002-7767-755X
- IdRef : 233502831
Orianne Wagner-Ballon
- Function : Author
- PersonId : 756203
- ORCID : 0000-0001-9071-6683
- IdRef : 079569668
Marie-Thérèse Rubio
- Function : Author
- PersonId : 19145
- IdHAL : marie-therese-rubio
- ORCID : 0000-0003-3732-5442
- IdRef : 149394489
Claude Preudhomme
- Function : Author
- PersonId : 762197
- ORCID : 0000-0002-1267-9546
- IdRef : 07342255X
Christophe Ferrand
- Function : Author
- PersonId : 757737
- ORCID : 0000-0003-0119-3919
Francine Garnache-Ottou
Connectez-vous pour contacter l'auteur
- Function : Correspondent author
- PersonId : 871184
Connectez-vous pour contacter l'auteur
Abstract
Neoplasms involving plasmacytoid Dendritic Cells (pDCs) include Blastic pDC Neoplasms (BPDCN) and other pDC proliferations, where pDCs are associated with myeloid malignancies: most frequently Chronic MyeloMonocytic Leukemia (CMML) but also Acute Myeloid Leukemia (AML), hereafter named pDC-AML. We aimed to determine the reactive or neoplastic origin of pDCs in pDC-AML, and their link with the CD34+ blasts, monocytes or conventional DCs (cDCs) associated in the same sample, by phenotypic and molecular analyses (targeted NGS, 70 genes). We compared 15 pDC-AML at diagnosis with 21 BPDCN and 11 normal pDCs from healthy donors. CD45low CD34+ blasts were found in all cases (10-80% of medullar cells), associated with pDCs (4-36%), monocytes in 14 cases (1-10%) and cDCs (2 cases, 4.8-19%). pDCs in pDC-AML harbor a clearly different phenotype from BPDCN: CD4+ CD56- in 100% of cases, most frequently CD303+, CD304+ and CD34+; lower expression of cTCL1 and CD123 with isolated lymphoid markers (CD22/CD7/CD5) in some cases, suggesting a pre-pDC stage. In all cases, pDCs, monocytes and cDC are neoplastic since they harbor the same mutations as CD34+ blasts. RUNX1 is the most commonly mutated gene: detected in all AML with minimal differentiation (M0-AML) but not in the other cases. Despite low number of cases, the systematic association between M0-AML, RUNX1 mutations and an excess of pDC is puzzling. Further evaluation in a larger cohort is required to confirm RUNX1 mutations in pDC-AML with minimal differentiation and to investigate whether it represents a proliferation of blasts with macrophage and DC progenitor potential.