Oh, what a surprise, another molecule causing trouble in the complex world of multiple myeloma (MM) – this time it’s the Fms-like tyrosine kinase 3 ligand (FLT3L) stealing the spotlight. Researchers, in their never-ending quest to unravel the mysteries of osteolytic lesions in MM, have stumbled upon FLT3L, which apparently likes to hang out in higher concentrations in the bone marrow and blood of MM patients, especially those with the added bonus of bone destruction.

So, they rounded up a small army of patients – 86 with MM, 306 with acute myeloid leukemia (AML), and 52 with acute lymphoblastic leukemia (ALL) – to play a game of “Whose Bone Marrow Has More FLT3L?” Spoiler alert: MM patients won by a landslide, especially those with the added accessory of bone lesions.

Then, in a twist that no one saw coming (except maybe everyone), they took this party to the petri dish. They treated some cells – HEK293T, HeLa, and U2OS, because variety is the spice of life – with FLT3L and watched the DKK1 transcript levels rise like dough in an oven, thanks to the helping hand of STAT3 phosphorylation. And just like a bad dance move, FLT3L treatment threw off the groove of WNT signaling and β-catenin’s grand entrance to the nucleus.

But wait, there’s more! A peek into the transcriptomic profiles revealed FLT3L and DKK1 were the life of the party in the hyperdiploidy subtype of MM. So, in a grand conclusion, FLT3L is not just a biomarker with a flair for predicting who’s going to have a bad time with their bones, but it might also be the next target for therapy – because, you know, we needed another target in the ever-growing list of potential treatments for MM.