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. 2024 Dec 10;8(23):6098-6103.
doi: 10.1182/bloodadvances.2024013801.

CYB5R3 T117S tempers fetal hemoglobin induction by hydroxyurea in patients with sickle cell disease

Fabliha A Chowdhury  1   2 , Malini Sharma  3 , Desiree Schafer  4 , Seyed M Nouraie  5 , Mark T Gladwin  6 , Adam C Straub  1   2   7 , Katherine C Wood  1   2
Affiliations

CYB5R3 T117S tempers fetal hemoglobin induction by hydroxyurea in patients with sickle cell disease

Fabliha A Chowdhury et al. Blood Adv. .
No abstract available

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Conflict of interest statement

Conflict-of-interest disclosure: A.C.S. received research funds from Bayer Pharmaceuticals and has an interest in Creegh Pharmaceuticals. The remaining authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Clinical data showing CYB5R3 T117S lessens the HbF, Hct, and total Hb responses to HU treatment in Walk-PHaSST patients. (A) Experimental design for clinical data analysis. (B) HbF (%) in patient samples by different CYB5R3 genotypes and HU treatment status, analyzed using a 2-way analysis of variance (ANOVA). (C-E) Hct (%) vs HbF (%) for the different CYB5R3 genotypes (x-axis truncated at 20% HbF; full-scale x-axis data available in supplemental Figure 1C-E), analyzed by simple linear regression. (F-H) Hb (g/L) vs HbF (%) for the different CYB5R3 genotypes (x-axis truncated at 20% HbF; full-scale x-axis data available in supplemental Figure 1F-H), analyzed by simple linear regression. The dotted lines in these figures show where the 2 lines meet, and the point of intersection is mentioned adjacent to the line. (I) Percentage of HbF in HUpos patient samples vs age for the different CYB5R3 genotypes analyzed by simple linear regression. Data are expressed as mean ± standard error of the mean unless otherwise specified. A comparison of the linear regression lines for the differences between slopes used a method equivalent to analysis of covariance (ANCOVA). A value of P < .05 was considered significant. In all correlation graphs, the P value is for the difference between the slopes in each graph. db SNP, single nucleotide polymorphism database; HUneg, HU untreated; HUpos, HU treated; MCV, mean corpuscular volume.
Figure 2.
Figure 2.
In vitro data showing CYB5R3 KO in CD34+ HSCs lessens the F cell response to HU treatment. (A) Experimental design for CD34+ HSC study. (B-C) Western blot and quantification of CYB5R3 protein on day 15, analyzed by Mann-Whitney nonparametric test. (D-E) Representative flow plots and quantification showing the percentage of HbF+ cells on day 18 in the HUneg and HUpos groups, analyzed by 2-way ANOVA. (F-G) Representative flow plots and quantification showing the percentage of CD44lowFSClow populations on day 18 in the HUneg and HUpos groups, analyzed by 2-way ANOVA. (H) HUpos/HUneg ratio of the CD44lowFSClow population in NT control and KO cells, analyzed by Mann-Whitney nonparametric test. Data are expressed as mean ± standard error of the mean. A value of P < .05 was considered significant. SSC, side scatter; FSC, forward scatter; HUneg, HU untreated; HUpos, HU treated. Fluorochromes: HbF-APC, CD44-PE-Cy7.
See this image and copyright information in PMC

References

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