Figure 3.
Tryptophan metabolism enzymes, kynurenine, and serotonin transporter gene expression during bone marrow transplant. Note the logarithmic scales. (A) Expression of TPH1, the rate-limiting enzyme responsible for conversion of tryptophan to serotonin, is elevated in patients with FA at both time points (baseline, 16.17 cycles [12.43-17.56] vs 20.52 cycles [18.97-21.93], P < .00001; day 14, 15.92 cycles [12.42-19.07] vs 22.33 cycles [20.15-23.16], P < .00001), with no significant change during transplant. (B) Production of kynurenine from tryptophan is significantly decreased in FA compared with other diagnoses at baseline (0.48 ng/mL [0.37-0.85] vs 1.09 ng/mL [0.79-1.28]; P = .0001) and remains low during transplant (0.48 ng/mL [0.37-0.85] vs 0.39 ng/mL [0.34-0.43]; P = .0048). (C) Expression of IDO, the rate-limiting enzyme responsible for conversion of tryptophan to kynurenine, is comparable in patients with and without FA at baseline (17.85 cycles [8.75-20.19] vs 17.51 cycles [15.98-18.51]; P = .51). At day 14, IDO decreases in patients without FA (17.51 cycles [15.98-18.51] vs 19.45 cycles [17.84-20.09]; P = .038), with no significant change during transplant in individuals with FA (17.85 cycles [8.75-20.19] vs 11.73 cycles [9.52-18.53]; P = .46). (D) Expression of SERT, a byproduct of SLC6A4 gene, is comparable between patients with and without FA at baseline (17.74 cycles [11.34-23.07] vs 19.16 cycles [16.57-21.58]; P = .33). SERT increases significantly in patients with FA by day 14 (17.74 cycles [11.34-23.07] vs 11.15 cycles [9.24-18.68]; P = .036) and is increased compared with patients without FA (11.15 cycles [9.24-18.68] vs 19.91 cycles [17.56-21.91]; P = .0014).