Role of Defects of Hematopoietic and Lymphoid Niches in Genesis of Chronic Lymphocytic Leukemia

Abstract

Background & Aims. Niche-forming elements of the bone marrow and lymphoid organs play an important role in the pathogenesis of chronic lymphocytic leukemias. The aim is to determine multifunctional characteristics of stromal elements of the hematopoietic and lymphoid microenvironment involved in formation of a niche of hematopoietic stem cells and lymphoid precursor cells. Methods. Histological specimens of the bone marrow and lymph nodes of 112 CLL patients (64 men and 48 women) were investigated. 45 patients were included in the combined analysis group. The age median was 60 years. 50 volunteers were included in the control group: trepanobiopsy of the iliac area was performed in 30 healthy subjects, and lymph node biopsy was performed in 20 patients with reactive lymphadenopathy. Standard staining (hematoxylin-eosin, azure-II-eosin, silver impregnation, Masson stain) was used for histological studies. The immunohistochemical analysis was performed using the primary antibody panel and the polymer visualization system Dako according to staining protocol. Results. While analyzing 96 trepanobioptates, we isolated three types of bone marrow infiltration: nodular (18.8 %, n = 18), interstitial (27 %, n = 26) and diffuse (54.2 %, n = 52). Nodular and interstitial bone marrow infiltrations reflect a more favorable course of CLL as compared to the diffuse type. The morphological characteristics of the bone marrow stroma of CLL patients may be caused by both primary impairment of the hematopoietic microenvironment, and cytokine disbalance resulting from the effect on the stroma of the leukemic clone. The morphological examination of lymph node bioptate of CLL patients demonstrated impairment of histoarchitectonics of lymphoid tissue elements in all cases. In lymph nodes of CLL patients, we demonstrated the increased number of small vessels on the background of decreased expression of extracellular matrix protein expression: IV type collagen, laminin, and desmin. Disintegration of lymph node follicular dendritic cells network was demonstrated. Conclusion. Examination of the nature of the effect of stroma on hematopoiesis remains an urgent hematological problem. In order to solve the problem of regulatory influence, the use of morphological methods is recommended, including the immunohistochemical analysis.