Aplastic anemia (AA) is a rare, immune-mediated hematopoietic disorder associated with significant morbidity and mortality [1]. AA can be diagnosed in patients presenting with pancytopenia and a hypocellular bone marrow. Typical symptoms include fatigue and easy bruising or bleeding; infections may be present, but generally there is no long-standing illness [2]. In patients with suspected AA, rapid and accurate diagnosis and concomitant supportive care are critical. Historically, immunosuppressive therapy (IST) and bone marrow transplantation (BMT) in eligible patients have been the mainstay of AA treatment [1]. In pediatric patients, new transplant strategies and improvements in supportive care have led to greatly improved outcomes and increasing use of BMT in both upfront and refractory settings [1, 3].
The incidence of AA varies with geography and it was found to be higher in Asia and lower in Europe, North America and Brazil according to the International Agranulocytosis and Aplastic Anemia Study [IAAAS] [4–7]. It was also identified that the incidence of that disease was 2-to 3-fold higher in Asia than in the West [8]. The great variation of the incidence of the disease is due to differential environmental exposure such as use of certain drugs and chemicals or by infectious agents such as viruses and bacteria. Besides the environmental agents the genetic background of different ethnic population may confer the risk of that disease [9–11]. It is really complicated to characterize the paediatric patients with aplastic anaemia than an adult because numerous inherited bone marrow failures can also present with aplastic anaemia without any obvious somatic features. Therfore, a precise diagnostic technique is essential for the children for the application of therapeutics [12]. Different demographic factors were already reported to be associated with aplastic anaemia among pediatric individuals and disease severity [13]. As the children are more sensitive to newer therapeutic agents in respect to their tolerability and suitability in contrast with chemotherapy or stem cell transplant, it’s necessary to establish and then incorporate into optimal treatment strategies.
Transcriptome analysis can clearly differentiate healthy controls from samples of AA patients. A study on transcriptome analysis among paediatric aplastic anaemia patients identified differentially expressed genes are involved in cell metabolism and cell communication or adhesion [14]. Fischer et al., 2012 able to identify that the transcription of major integrins was dramatically down-regulated in the few remaining CD34+ bone marrow cells from children with severe aplastic anaemia [15]. MSCs usually resides within the stroma and they are derived from bone marrow. They play significant role in hematopoiesis and immunomodulation. Various studies have reported the differential gene expression in MSCs among patients with aplastic anaemia compared to healthy controls. A study by Li et al., 2012 identified over 300 differentially expressed genes among aplastic anaemia compared with healthy controls [16]. These differentially expressed gene are involved in apoptosis, adipogenesis, and the immune response. Another study also reported increased MSC apoptosis in AA patients [17]. Consequent studies also revealed that MSCs among AA patients have lower proliferation potential [18, 19].
Various studies have already reported gene expression profiling of bone marrow MSCs from aplastic anaemia patients and they identified several genes those are involved in various biological processes such as cell cycle, cell division, proliferation, chemotaxis, adipogenesis-cytokine signalling and haematopoietic cell lineage differentiation which suggests that impaired cellular function is a hallmark of this disease [20–22]. It is well documented in several studies that transcription factor deregulation were also involved in aplastic anaemia. It was reported that GATA2 transcription factor downregulation in bone marrow MSCs can accelerate adipocyte differentiation which is one of the chief characteristics of aplastic anaemia [23].
Therefore, we undertook the current study to determine the deregulated genes associated with pediatric patients with aplastic anaemia and their transcription factor binding motifs which can regulate this disease progression.