Chomel Jean-Claude, Aggoune Djamel, Sorel Nathalie, Turhan Ali G
Service de cancérologie biologique, CHU de Poitiers, Poitiers, France - Inserm U935, université de Poitiers, France.
Inserm U935, université de Poitiers, France.
Med Sci (Paris). 2014 Apr;30(4):452-61. doi: 10.1051/medsci/20143004022. Epub 2014 May 5.
The physiological hematopoietic niche located in bone marrow is a pluricellular structure whose components are now well identified. Within this microenvironment, hematopoietic stem cells are in direct contact with mesenchymal stromal cells, osteoblasts and sinusoidal endothelial cells. These close relationships drive specialized cellular functions (proliferation/quiescence, differentiation/self-renewal) ensuring an efficient hematopoiesis. Chronic myeloid leukemia (CML) is a major model of leukemic hematopoiesis. The BCR-ABL1 tyrosine kinase, constitutively activated in CML, plays a critical role in the pathogenesis of the disease. An intensive cross-talk between CML progenitors and the components of the hematopoietic niche has recently been demonstrated. Consequently, the occurrence of the so-called leukemic niche promotes both the proliferation of myeloid cells and the maintenance of quiescent leukemic stem cells. This bone marrow niche could also protect CML stem cells from tyrosine kinase inhibitors and probably contribute to their resistance towards targeted therapies.
位于骨髓中的生理性造血微环境是一种多细胞结构,其组成部分现已明确。在这个微环境中,造血干细胞与间充质基质细胞、成骨细胞和窦状内皮细胞直接接触。这些紧密关系驱动着特定的细胞功能(增殖/静止、分化/自我更新),确保有效的造血过程。慢性髓性白血病(CML)是白血病造血的主要模型。在CML中持续激活的BCR-ABL1酪氨酸激酶在该疾病的发病机制中起关键作用。最近已证实CML祖细胞与造血微环境的组成部分之间存在强烈的相互作用。因此,所谓白血病微环境的出现既促进了髓系细胞的增殖,也维持了静止的白血病干细胞。这种骨髓微环境还可能保护CML干细胞免受酪氨酸激酶抑制剂的影响,并可能导致它们对靶向治疗产生耐药性。