Complement or insult: the emerging link between complement cascade deficiencies and pathology of myeloid malignancies

Area of Science:

• Immunology
• Oncology
• Hematology

Background:

• The complement cascade is a vital immune system component with established roles in solid tumors.
• Its involvement in the cancer microenvironment influences immune, cancer, and stromal cells, contributing to inflammation-driven neoplasms.
• However, the complement cascade's specific role in hematological malignancies, particularly myeloid ones, remains largely unexplored.

Purpose of the Study:

• To review and summarize the identified links between complement cascade involvement and the pathobiology of myeloid malignancies.
• To highlight the impact of complement deficiencies on myeloid neoplasms.
• To underscore the connection between complement, inflammation, and hematopoietic system homeostasis.

Main Methods:

• Literature review focusing on complement cascade involvement in myeloid malignancies.
• Analysis of existing evidence on the effects of complement deficiencies (initiators, mid- and terminal-components, inhibitors) on myeloid neoplasms.
• Synthesis of findings to elucidate the mechanistic links.

Main Results:

• Accumulating evidence suggests elevated complement cascade activity in the cancer microenvironment.
• Complement deficiencies are associated with increased risks of infections, inflammation, and thrombosis.
• The review consolidates current knowledge on complement's role in myeloid cancer pathobiology.

Conclusions:

• The complement cascade plays a significant role in the development, progression, and relapse of myeloid malignancies.
• Links between complement cascade, inflammatory signaling, and hematopoietic system homeostasis are evident.
• Further research is needed to fully detail the mechanistic involvement of the complement cascade in myeloid cancer development and progression.