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NBME 18 Answers

nbme18/Block 4/Question#4 (32.8 difficulty score)
36 yo woman, 2 weeks of fatigue, bleeding ...
Histone acetylaseπŸ”
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 +8 
submitted by sympathetikey(1357),
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Hstnoei enatltoaciy wlsaol for rnaaoxeitl of the NDA os htat tiaporctnsinr acn co.rpeed All rtasn riienotc daic auecss eht lteausonyrgc ni MAPL to rfehtru uteram, icwhh eriqresu AND pitcitrnaonsr / t.rintlosana

osler_weber_rendu  The questions asks for response to ATRA. Should that not be decreased transcription to treat the cancer? Which makes methyl transferase (aka methylation) the more likely answer +6  
pg32  @osler, no @sympathetikey is correct. ATRA's mechanism in treating APML is to encourage the cells to mature. Maturation would require gene transcription, meaning histone acetylases would be used. +3  
nnp  but ATRA is letting transcription of an abnormal protein ( that is 15:17 translocation) +2  
lowyield  i believe the mechanism of APML is that the compound protein is ineffective at allowing for maturation of the blasts. giving ATRA allows the blasts to circumnavigate this step, relieving the backup +10  



 +1 
submitted by banana(15),

I thought (incorrectly, obviously) that histone kinase also allowed transcription to proceed?

banana  Just kidding, dead wrong: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3469451/ histone-P demarcates DNA breakage for repair +1  
utap2001  function histone kinase The best-known function of histone phosphorylation takes place during cellular response to DNA damage, when phosphorylated histone H2A(X) demarcates large chromatin domains around the site of DNA breakage. function of histone N-methyltransferase methyltransferases (HMT) are histone-modifying enzymes (e.g., histone-lysine N-methyltransferases and histone-arginine N-methyltransferases), that catalyze the transfer of one, two, or three methyl groups to lysine and arginine residues of histone proteins. Histone methylation is a principal epigenetic modification of chromatin[9] that determines gene expression, genomic stability, stem cell maturation, cell lineage development, genetic imprinting, DNA methylation, and cell mitosis. +