To most CLL patients Acute Myeloid Leukaemia (AML) will be an unfamiliar disease. Rather than the B lymphocytes we know and love to hate, the cancerous cells in AML are immature myeloid cells, proliferating to crowd out healthy blood cells in the bone marrow. AML progresses rapidly and the prognosis is often poor, though as a heterogenous disease AML's treatability in a given case has depended on which genetic variants are involved cancer.org/cancer/types/acu...
Here we come to a direct connection between AML and CLL. As noted in the above reference, having a blood disorder such as a myelodysplastic syndrome (MDS) that led to AML is linked to a worse outlook; also AML that develops after a person is treated for another cancer with chemotherapy or radiation therapy tends to have a worse outlook. The risks of treatment-induced MDS, and of subsequent AML, are the principal reasons why FCR - a chemoimmunotherapy - has been superseded by non-chemo therapies as first-line treatment of choice for CLL in the more advanced healthcare systems of the world. Even though FCR offers the prospect of a "functional cure" to around half of patients with M-CLL (i.e. CLL with mutated IGHV), treatment with FCR can cause prolonged suppression of bone marrow function and statistically carries a 6 percent cumulative risk of contracting MDS ashpublications.org/blood/a...
Now we come to the good news: Although genetically heterogenous, AMLs are universally characterized by a prominent differentiation block that disrupts normal myeloid maturation and promotes leukaemia cell self-renewal. "Differentiation arrest", a manifestation of the clinical phenotype, represents an AML vulnerability that can be leveraged for therapeutic purposes. The authors of nature.com/articles/s41586-... have done just that, overcoming differentiation arrest and enabling myeloid cells to reach maturity without becoming cancerous, in mice and in human cells in vitro. If the authors mean what they imply, that this therapy should be effective across all genetic variants of AML, it really is a breakthrough.
This article insideprecisionmedicine.com... gives a more readable summary of the research. It concludes with: "By targeting the fundamental block in cell maturation that defines AML, this strategy could help transform treatment for a disease that currently has a median survival of less than nine months. As the authors concluded, the findings offer “compelling evidence to support the testing of this combination therapy in AML patients.” Promising news for those of us treated with FCR.
