Plasmacytoid Dendritic Cell Infiltration in Acute Myeloid Leukemia

Abstract

Introduction: Increasing evidence has demonstrated that plasmacytoid dendritic cells (PDCs) in the tumor microenvironment (TME) play an important role in tumorigenesis and progression. PDC infiltration has been found in certain malignancies such as classic Hodgkin's lymphoma and chronic myelomonocytic leukemia. Our previous work reported that PDC infiltration could occur in acute myeloid leukemia (AML), but the clinical significance of PDC in AML has not been thoroughly investigated.

Patients and methods: Here, we evaluated the clinical significance of PDC to AML transition in a leukemia microenvironment. The frequency of PDCs in 80 acute myelomonocytic leukemia (AML-M4) and 83 acute monocytic leukemia (AML-M5) patients was determined by flow cytometry.

Results: We found 62 cases with PDC infiltration. These patients showed higher numbers of bone marrow blasts, higher mean Hb concentration, and required more cycles of chemotherapy before achieving complete remission (CR), but had lower white blood cell and platelet counts compared to patients without PDC infiltration. Drug sensitivity analysis showed that patients with PDC infiltration had lower sensitivity to standard chemotherapy regimens. Kaplan-Meier survival curves demonstrated that patients with PDC infiltration had a shorter overall survival (OS) time and progression-free survival time.

Discussion: These results suggested that PDC infiltration can be used for risk stratification of AML-M4/M5, and PDCs may transdifferentiate into leukemia in an AML microenvironment.

Keywords: acute myeloid leukemia; AML; hematopoietic stem cell transplantation; prognosis; tumor-forming plasmacytoid dendritic cells; TF-PDCs.

Figure 1

Radar plots illustrate cell composition of leukemic bone marrow. TF-PDCs in this sample are indicated by the blue cluster (Lin-HLA-DRbri+CD123bri+CD304+CD56+CD11c-CD13+CD33+CD15-CD14-CD64-CD34-CD117-CD38+); myeloid progenitor cells comprise the red cluster (CD34bri+CD38+CD117+HLA DR+CD123+CD56par+CD13+CD33bri+CD64par+CD14-CD11b-); monocytic cells are pink clusters; mature lymphoid cells are green.

Figure 2

Chromosomal abnormality of TF-PDCs in AML patients. (A) AML1 amplification. Red probe is ETO; green probe is AML1. (B) BCR amplification. Red probe is ABL; green probe is BCR. (C) CBFB-MYH11 fusion. Red probe is CBFb; green probe is MYH11; yellow signal indicates fusion. (D) 5q-, CSF1R (5q33) and EGR1 (5q31) are red probe; D5S23 and D5S721 (5p15) are green probe. (E) MLL amplification. MLL (11q23)5ʹ terminal is green probe; MLL (11q23)3ʹ is red probe. (F) ETO amplification. Red probe is ETO; green probe is AML1.

Figure 3

Drug sensitivity analyzed by HDGS. (A) The inhibition ratio of leukemia cells to chemotherapy drugs. (B) The inhibition ratio of leukemia cells to assistance therapy drug. (C) The inhibition ratio of leukemia cells to targeted drugs. (D) The inhibition ratio of leukemia cells to normal therapy regimens. (E) Serial monitoring of the percentage of blast cells and PDCs in patients. (F) Cell cycle was evaluated by flow cytometry in PDC cells.

Figure 4

Kaplan–Meier estimated overall survival of (A) the entire patient cohort (patients with HCT excluded) stratified by TF-PDC positive and negative. Kaplan–Meier estimated overall survival (B) of the entire patient cohort stratified by chemotherapy group and allo-HSCT. Kaplan–Meier estimated overall survival of TF-PDC positive AML patient cohort (C) and TF-PDC negative patients (D) stratified by chemotherapy group and allo-HSCT, Kaplan–Meier estimated relapse free survival (E) and cumulative incidence of relapse (F).