Abstract
Bone marrow (BM) is a highly complex tissue that provides important regulatory signals to orchestrate hematopoiesis. Resident and transient cells occupy and interact with some well characterized niches to produce molecular and cellular mechanisms that interfere with differentiation, migration, survival, and proliferation in this microenvironment. The acute myeloid leukemia (AML), the most common and severe hematological neoplasm in adults, arises and develop in the BM. The osteoblastic, vascular, and reticular niches provide surface co-receptors, soluble factors, cytokines, and chemokines that mediate important functions on hematopoietic cells and leukemic blasts. There are some evidences of how AML modify the architecture and function of these three BM niches, but it has been still unclear how essential those modifications are to maintain AML development. Basic studies and clinical trials have been suggesting that disturbing specific cells and molecules into the BM niches might be able to impair leukemia competencies. Either through niche-specific molecule inhibition alone or in combination with more traditional drugs, the bone marrow microenvironment is currently considered the potential target for new strategies to treat AML patients. This review describes the cellular and molecular constitution of the BM niches under healthy and AML conditions, presenting this anatomical compartment by a new perspective: as a prospective target for current and next generation therapies.
Highlights
The bone marrow (BM) is a soft and viscous tissue within the bone cavities that holds a highly complex and dynamic microenvironment
While acute myeloid leukemia (AML) as a whole are treated with 7 + 3 protocol, patients diagnosed with low-risk Ate promyelocytic leukemia (APL) receive induction treatment with arsenic trioxide plus all-trans retinoic acid (Burnett et al, 2015), which leads to disease remission with excellent results in terms of overall survival (Wang and Chen 2008)
Experiments involving Opn-knockout mice reported a significant increase in hematopoietic stem cells (HSC) cycling, suggesting that, under normal conditions of osteopontin expression, this molecule acts as a negative regulator of stem cell pool size, actively maintaining the quiescence of these cells by inhibiting the entry of HSCs into the cell cycle and, blocking cell proliferation (Nilsson et al, 2005; Stier et al, 2005)
Summary
Débora Bifano Pimenta†, Vanessa Araujo Varela†, Tarcila Santos Datoguia, Victória Bulcão Caraciolo, Gabriel Herculano Lopes and Welbert Oliveira Pereira *. Resident and transient cells occupy and interact with some well characterized niches to produce molecular and cellular mechanisms that interfere with differentiation, migration, survival, and proliferation in this microenvironment. The acute myeloid leukemia (AML), the most common and severe hematological neoplasm in adults, arises and develop in the BM. Basic studies and clinical trials have been suggesting that disturbing specific cells and molecules into the BM niches might be able to impair leukemia competencies. Either through niche-specific molecule inhibition alone or in combination with more traditional drugs, the bone marrow microenvironment is currently considered the potential target for new strategies to treat AML patients. This review describes the cellular and molecular constitution of the BM niches under healthy and AML conditions, presenting this anatomical compartment by a new perspective: as a prospective target for current and generation therapies
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