The Profile of T Helper Subsets in Bone Marrow Microenvironment Is Distinct for Different Stages of Acute Myeloid Leukemia Patients and Chemotherapy Partly Ameliorates These Variations.

BACKGROUND

T helper (Th) cells immune regulation is important for the pathogenesis of acute myeloid leukemia (AML). Recurrent Th abnormalities in AML peripheral blood were reported, while the comprehensive status of various Th subsets is rarely investigated in bone marrow (BM) microenvironment which is the origin of AML leukemic blast cells.

METHODS

BM was extracted from 48 newly-diagnosed (ND), 34 complete-remission (CR), 19 relapsed-refractory AML patients and 15 controls. Slight iron deficiency anemia patients were used as controls. Th subsets frequencies were examined by flow cytometry. BM plasma Th-associated cytokines levels were determined by ELISA. The expression of key transcription factor was examined by RT-PCR.

RESULTS

Th22, Th17, Th1, Th2 cells, IL-22 and RORC expression were significantly decreased, while Treg cells, related cytokine IL-10 and transcription factor Foxp3 were markedly elevated in ND compared to CR patients or controls. Meanwhile, the imbalanced Th1/Th2 and Th17/Treg ratio were observed in ND and relapsed-refractory patients. Negative correlation between Th1 or Th2 and peripheral WBC, between Th17/Treg or Th1/Th2 and leukemic blast existed in ND patients. Moreover, chemotherapy ameliorated these variations.

CONCLUSION

Th subsets in BM are distinct for different stages of AML and chemotherapy partly ameliorates the abnormality. Our findings suggest that these cells and cytokines may be implicated in AML pathogenesis and provided therapeutic insights.