Leukemia
Haemopoiesis is the formation of blood cells and most of the blood cells form in the bone marrow. The cancer of blood cells is called leukemia. In leukemia, cancerous blood cells form and crowd out the healthy blood cells in the bone marrow. Depending upon the type of cells that has become cancerous, the leukemia can be of different types (eg: lymphoid leukemia, myeloid leukemia etc.). Leukemia occurs most often in elderly population (older than 55 years), and also it is the most common cancer in children (younger than 15 years). Leukemia is either acute (fast growing) or chronic (slow-growing). The treatment and prognosis for leukemia depend on the type of blood cell affected and whether the leukemia is acute or chronic. Chemotherapy is often used to treat leukemia.
The acute leukemias are a heterogeneous group of serious malignant disorders that are characterized by the uncontrolled clonal expansion and transformation of hematopoietic progenitor cells in the thymus or bone marrow. Although these cells are no longer able to differentiate and mature, their capacity to divide remains, resulting in a rapidly expanding pool of abnormal cells that accumulate in the blood, invade and damage vital organs and replace normal marrow tissue and hematopoietic precursor cells, leading to bone marrow failure. The disease is characterized as either acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML), on the basis of cytochemical, immunophenotypic, morphological and genetic testing.
Current Focus
Development of bone marrow niche for drug screening applications in AML
AML is a heterogeneous clonal disorder marked by the accumulation of undifferentiated myeloid blasts. AML is thought to arise from a continuously replenishing rare and functionally distinct leukaemic stem and progenitor cell (LSPC) population characterized by its capacity of self-renewal and generation of leukaemic progenitors. In AML, as in normal haematopoiesis, self-renewal capacity has been identified within the phenotypically immature CD34+CD38-subset. It has been shown that the CD34+CD38- LSPC burden at diagnosis correlates with minimal residual disease frequency and poor overall survival in AML. The bone marrow microenvironment provides a highly favourable site for the growth, differentiation and survival of haematopoietic cells. Bone marrow stroma provides adhesion receptors, secreted extracellular matrix and both secreted and membrane bound haematopoietic cytokines. Expression of cell adhesion and cytokine receptors by AML cells has been associated with relapse, supporting the notion that it is not just the leukaemia cells themselves but interactions with their microenvironment that underpin cell survival. We provide evidence that in vitro system featuring some of the constituents of the bone marrow microenvironment, namely fibronectin with a cocktail of cytokines such as IL-3, IL-6, SCF and Ang-1 supports survival of leukemic cells (Mony et al., 2008; Jawad et al., 2010)
Now the aim of our lab is to develop a 3D-Bone marrow niche like condition for testing the chemo-sensitivity of leukaemic stem and progenitor cells (Maya et al., 2015). This will help to study the effect of niche on drug sensitivity and also in identifying novel agents that have the potential to target leukaemic stem cells in their microenvironment will aid in the characterization of candidate agents for post-remission chemotherapy.
