Histopathological changes of bone marrow in patients with autosomal recessive osteopetrosis and mutation in TCIRG1 gene

Abstract

Osteopetrosis is a group of rare hereditary diseases, the general structural manifestation of which is the excessive volume of bone tissue due to violation of osteoclastic resorption. The only way to treat this group of patients so far remains transplantation of hematopoietic stem cells, but the degree of its effectiveness largely depends on the severity of morphological changes in the hematopoietic microenvironment in the bone marrow. In this regard, a comprehensive clinical and morphological analysis, in conjunction with the results of transplantation can help in determining the prognosis of the disease depending on the genetic type of osteopetrosis. The material for the studies were biopsies and smears of bone marrow of patients with osteopetrosis, who were received at the R. Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation from the republics of Chuvashia and Mari El for carrying out transplantation of hematopoietic stem cells. The histological preparations were stained with hematoxylin and eosin, azur by Romanovsky and by Van Gieson. Bone marrow smears were stained by Romanovsky-Giemsa. The presence of the mutation c.807 + 5G>A in the gene TCIRG1 in patients with autosomal recessive osteopetrosis causes a complete loss of osteoclastic resorption, which is accompanied by pronounced early structural changes in the hematopoietic microenvironment already at the time of diagnosis. This is manifested by an excessive amount of lamellar bone at the same time as the almost complete obliteration of the medullar lacunae, as well as fibrosis of the bone marrow stroma. A common morphological phenomenon among this group of patients is the presence in the bone marrow of an excessive number of osteoclast differentiation cells without the formation of resorption lacunae. This causes a complete suppression of hemopoiesis, which clinically manifests cytopenia and the formation of foci of extramedullary hematopoiesis. Such pronounced structural changes in the hematopoietic microenvironment result in a high risk of primary graft failure during after transplantation of bone marrow hematopoietic stem cells, the effectiveness of which decreases as the child's age increases. Early development of pronounced structural changes in the hematopoietic microenvironment in patients with TCIRG1-mediated osteopetrosis determines the need for diagnosis and transplantation as soon as possible after birth.