For some researchers, there can be a significant gap between the results of their applied research and the subsequent implementation into patient treatment and care. Working closely with clinicians can lead to direct feedback loops between such research projects and patient outcomes.
Ximbio spoke to Disha Malani, a doctoral researcher at the University of Helsinki to find out about her experience:
Future proofing Acute Myeloid Leukaemia treatment
Disha’s current research is part of a collaborative project involving clinicians, bioinformaticians and researchers, which aims to identify molecular biomarkers for drug sensitivity and resistance to approved targeted drugs, with a single objective of creating personalised treatments for Acute Myeloid Leukaemia (AML) patients. For this, AML cell lines that were resistant to varying concentrations of the commonly used chemotherapeutic agent, cytarabine were generated. In this disease model, the underlying mechanism of cytarabine resistance was studied.
“Our project has a real time impact on leukaemia patient treatment. So it's really great that we can actually help to improve the overall survival of the patients, which I think is something that researchers would aim for, that their research has an outcome in someone's life. So that has been really inspiring and exciting”
The findings from the model provided evidence for repurposing glucocorticoid drugs to treat cytarabine-resistant AML. Interestingly, Disha’s efforts to generate cytarabine-resistant variants of commonly used AML cell lines, SHI-1 and MOLM-13, allowed her to find consistencies between in vitro and in vivo sensitivity to glucocorticoids. SHI-1 has a wild-type FLT3 gene and can be used to observe glucocorticoid sensitivity. MOLM-13 has a mutation in the FLT3 gene and no glucocorticoid sensitivity is seen. In 66 ex vivo chemo-refractory samples from cytarabine-treated AML patients this same trend was seen, cementing the FLT3 gene as an important part of personalising treatment in cytarabine-resistant AML cases.
“Imagine a person’s life could be improved by four months with a drug.”
Schematic diagram illustrating generation of cytarabine-resistant AML cell line variants from Malani et al, 2017. Leukemia
A focus on research translation
The research papers published during this project have generated widespread interest with the articles being cited multiple times. This has led to multiple requests for access to the cytarabine-resistant cell lines created. For Disha, sharing the research materials globally has been an important focus throughout her research career so far, however, like many researchers, she wasn’t sure of the procedures or channels to make her research tools available to other scientists.
“I think research or science is a community-based effort and it should be done in such a way that every material and every information should be shared to progress faster.”
She approached the University of Helsinki invention services (HIS) for assistance. Through HIS’s existing partnership with Ximbio, all MTA requests are now being fulfilled by Ximbio on her behalf, from production to necessary logistics.
“We got several requests from other researchers asking for these models, but thanks to Ximbio now it's easily doable because when we tried in past to do it ourselves, it proved difficult - we got stuck with the regulatory approvals and material transfer agreements. Now, we commercialised the cell lines with Ximbio and they manage all the logistics and related regulatory aspects, so I'm very happy.”