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FEATURES OF STROMAL ELEMENTS OF HEMATOPOIETIC BONE MARROW NICHE IN MULTIPLE MYELOMA
Author(s): ,
N. Yu. Semenova
Affiliations:
Russian research institute hematology and transfusiology,Saint-Petersburg,Russian Federation
,
S.S. Bessmeltsev
Affiliations:
Russian research institute hematology and transfusiology,Saint-Petersburg,Russian Federation
V.I. Rugal
Affiliations:
Russian research institute hematology and transfusiology,Saint-Petersburg,Russian Federation
(Abstract release date: 05/18/17) EHA Library. Semenova N. 05/18/17; 182660; PB1946
Ms. Natalya Semenova
Ms. Natalya Semenova
Contributions
Abstract

Abstract: PB1946

Type: Publication Only

Background

Structure of bone marrow stroma – mesenchymal stromal cells (MSC), endosteal stromal cells, and microvessels forming the hematopoietic niche and regulate the development of hematopoietic stem cells (HSC). Analysis of morphological changes of these elements of the hematopoietic niche is important to clarify the pathogenesis of multiple myeloma (MM).

Aims

To investigate the morphological and functional characteristics of stromal elements of the hematopoietic niche in bone marrow of patients with MM, as well as the characteristics of culture of mesenchymal stromal cells (MSC) and hematopoietic stem cells (HSC).

Methods
42 trepanobiopsy of bone marrow from patients diagnosed with MM were used for the study. The age of the patients ranged from 53 to 72. The study applied histological, histochemical, immunohistochemical (IHC) and morphometric methods (VideoTest®). Also 20 patients from this group conducted cultural studies for the determination of colony-forming ability of HSC and morphofunctional status of MSC.

Results
Myeloma cellular composition of infiltrates were polymorphic. The surveyed patients were allocated to 3 types of infiltration is nodular, interstitial, diffuse. The histogenesis of infiltration was confirmed by IHC research with antibodies 79α, CD 138, CD 38.Regardless of the type of infiltration in all patients were recorded focal destructive changes of bone tissue. The density of microvessels in IHC studies with antibodies to CD 31, CD34 cl.II (Dako) was increased. A greater number of microvessels were detected in the endosteal area at all types of the bone marrow involvement (compared to normal), the total number of microvessels could statistically do not exceed such normal. A reduction in the expression of type I collagen bone matrix and the increase of collagen type IV expression, which is associated with increased microvascular density. Intratrabecular collagen type I was mellowed, ossification was reduced, most notably it revealed in areas of trabecules resorption. At the same time increased the amount of collagen type IV in endosteal spaces of the bone marrow. A typical feature was the appearance of focal network of reticulin fiber in subendosteal and perivascular spaces.Cultural studies have shown a significant decrease of colony-forming ability of HSC mobilized peripheral blood of MM patients after cryopreservation. In vitro studies preliminary data on lack of differences in the phenotype of MSC bone marrow of patients with MM and phenotype from healthy individuals, but also, a decrease in the proliferative ability of the MSC of patients with MM.

Conclusion
Analysis of parenchymal-stromal relationships in trepanobiopsy bone marrow of patients with MM evidence of their violation in the context of malignancy of lymphopoiesis, while cultural studies have shown a decrease of colony-forming ability of HSC and proliferative capacity of MSC. Regardless of the prevalence of neoplastic lesions, and myeloma infiltration noted the response of the stromal microenvironment, forming the hematopoietic niche.

Session topic: 13. Myeloma and other monoclonal gammopathies - Biology

Keyword(s): Multiple Myeloma, Microenvironment, Mesenchymal cells

Abstract: PB1946

Type: Publication Only

Background

Structure of bone marrow stroma – mesenchymal stromal cells (MSC), endosteal stromal cells, and microvessels forming the hematopoietic niche and regulate the development of hematopoietic stem cells (HSC). Analysis of morphological changes of these elements of the hematopoietic niche is important to clarify the pathogenesis of multiple myeloma (MM).

Aims

To investigate the morphological and functional characteristics of stromal elements of the hematopoietic niche in bone marrow of patients with MM, as well as the characteristics of culture of mesenchymal stromal cells (MSC) and hematopoietic stem cells (HSC).

Methods
42 trepanobiopsy of bone marrow from patients diagnosed with MM were used for the study. The age of the patients ranged from 53 to 72. The study applied histological, histochemical, immunohistochemical (IHC) and morphometric methods (VideoTest®). Also 20 patients from this group conducted cultural studies for the determination of colony-forming ability of HSC and morphofunctional status of MSC.

Results
Myeloma cellular composition of infiltrates were polymorphic. The surveyed patients were allocated to 3 types of infiltration is nodular, interstitial, diffuse. The histogenesis of infiltration was confirmed by IHC research with antibodies 79α, CD 138, CD 38.Regardless of the type of infiltration in all patients were recorded focal destructive changes of bone tissue. The density of microvessels in IHC studies with antibodies to CD 31, CD34 cl.II (Dako) was increased. A greater number of microvessels were detected in the endosteal area at all types of the bone marrow involvement (compared to normal), the total number of microvessels could statistically do not exceed such normal. A reduction in the expression of type I collagen bone matrix and the increase of collagen type IV expression, which is associated with increased microvascular density. Intratrabecular collagen type I was mellowed, ossification was reduced, most notably it revealed in areas of trabecules resorption. At the same time increased the amount of collagen type IV in endosteal spaces of the bone marrow. A typical feature was the appearance of focal network of reticulin fiber in subendosteal and perivascular spaces.Cultural studies have shown a significant decrease of colony-forming ability of HSC mobilized peripheral blood of MM patients after cryopreservation. In vitro studies preliminary data on lack of differences in the phenotype of MSC bone marrow of patients with MM and phenotype from healthy individuals, but also, a decrease in the proliferative ability of the MSC of patients with MM.

Conclusion
Analysis of parenchymal-stromal relationships in trepanobiopsy bone marrow of patients with MM evidence of their violation in the context of malignancy of lymphopoiesis, while cultural studies have shown a decrease of colony-forming ability of HSC and proliferative capacity of MSC. Regardless of the prevalence of neoplastic lesions, and myeloma infiltration noted the response of the stromal microenvironment, forming the hematopoietic niche.

Session topic: 13. Myeloma and other monoclonal gammopathies - Biology

Keyword(s): Multiple Myeloma, Microenvironment, Mesenchymal cells

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