Smoke poured out of the two-story building on 72-10 Myrtle Avenue in Glendale just before 9.
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The multi-purpose building contains a Farmer's Market grocery store on the first floor as well as an equipment store.
Nearly 200 firefighters responded to the scene.
Two firefighters suffered serious injuries.
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The FDNY brought the fire under control at about 1 a.m. and continued putting out hot spots for several more hours.
The building appeared to be a total loss.
The cause of the blaze is under investigation.