Off-label drug Metformin may have a role in Myeloid Leukaemia where it causes generation of healthy bone marrow fat and this in turn creates more healthy blood cells, suppressing the leukaemia cells by 'crowding them out’.
Patients with Acute Myeloid leukaemia have ta conundrum. Their first need is obviously to kill the cancerous leukaemia cells. Standard leukaemia treatments focus on this. However, as the anti-cancer treatment progresses, healthy red blood cell production declines and anaemia and infection ensue, even leading to fatality.
The fact is that, historically, myeloid leukaemia treatments have failed to pay any attention to the need for bolstering healthy red blood cells.
AML vs CML difference
Acute Myeloid Leukaemia (AML) starts in the bone marrow, where new blood cells are made, but rapidly progresses into the blood and then on to the spleen, lymph nodes, liver and other organs.
Chronic Myeloid Leukaemia tends to be slow growing and so more likely to build up in the bone marrow first, although it does move into the blood and then the organs. The difference between AML and CML is largely to do with the speed at which they develop and worsen.
McMaster researchers take a different approach
In 2017, researchers from McMaster Stem Cell and Cancer Research Institute decided to look at the bone marrow as a single ecosystem, considering both the diseased and the healthy cells. This study (1) was largely undertaken because of a lack of advancement in treatment options and the view from the research team that a completely new approach was required.
Bone marrow is known to accumulate fat cells, but not the same as subcutaneous fat or visceral fat. This fat controls the health of the bone marrow. These fat cells, or adipocytes, are not energy stores but derived from stem cells rather like osteoblasts occur in the bones themselves; and they have an important function - they promote the generation of stem cells and new red blood cells (2).
‘Surprising’ action of Metformin
Mick Bhatia, a director and senior scientist with the McMaster Stem Cell and Cancer Research Institute, led the group that performed the three and a half year study. Having collected bone marrow samples from three different medical centres, the drug they used was the diabetes drug Metformin, normally used to cut blood sugar.
In this study, metformin (which is known to increase the generation of bone marrow fat), surprised the scientists as it was shown to activate red blood cell generation in the bone marrow, resulting in the cancer cells being suppressed and crowded out.
The researchers concluded that Metformin offered the opportunity to be used in conjunction with other treatments, or even on its own.
Go to: Review of Metformin as an off-label cancer drug
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References
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Acute myeloid leukaemia disrupts endogenous myelo-erythropoiesis by compromising the adipocyte bone marrow niche; Allison L. Boyd et al; Nature Cell Biology, 2017;
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Bone marrow adipocytes promote the regeneration of stem cells and haematopoiesis by secreting SCF; Bo O Zhou et al; Nature Cell Biology, 2017 Aug;19(8):891-903.
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