Figure 1.
Early B-cell development is suppressed in the bone marrows of patients with HLH. (A) The individual percentages of CD19+ (B-cell lineage), CD3+ (T-cell lineage), and CD33+ (myeloid lineage) cells in the bone marrow compartment for age-matched healthy control (HC) group (n = 8), P-HLH group (n = 5), I-HLH group (n = 19), and R-HLH group (n = 12). B-cell compartment (HC, 16.59% ± 1.85%; P-HLH, 10.78% ± 4.05%; I-HLH, 6.04% ± 1.19%; and R-HLH, 3.64% ± 0.76%); T-cell compartment (HC, 11.16% ± 1.01%; P-HLH, 28.38% ± 4.36%; I-HLH, 18.21% ± 2.48%; and R-HLH, 14.78% ± 3.36%); myeloid compartment (HC, 4.20% ± 0.62%; P-HLH, 8.93% ± 1.84%; I-HLH, 8.02% ± 1.09%; and R-HLH, 5.95% ± 1.07%). (B) Percentage of hematopoietic stem and progenitor cells (CD34+CD38−) population in the bone marrow compared among HC (n = 8; 0.17% ± 0.06%), P-HLH (n = 3; 0.055% ± 0.04%), I-HLH (n = 4; 0.024% ± 0.005%), and R-HLH (n = 4; 0.096% ± 0.04%). (C) Percentage of HPC (CD34+CD38+) population in the bone marrow compared among HC (n = 8; 2.94% ± 0.19%), P-HLH (n = 3; 1.87% ± 0.63%), I-HLH (n = 4; 1.90% ± 0.48%), and R-HLH (n = 4; 0.90% ± 0.49%) groups. (D) Percentages of pre–pro-B cells (CD34+CD19−CD10+) in HC (n = 8; 0.12% ± 0.03%) and HLH (n = 7; 0.0047% ± 0.0020%) groups and (E) pro-B cells (CD34+CD19+CD10+) in in the bone marrow of HC (n = 8; 1.26% ± 0.13%) and HLH (n = 7; 0.023% ± 0.017%) groups. (F) Representative flow cytometry dot plot of CD19/CD45 showing the depletion of hematogones (CD19+CD45+) in a patient with P-HLH (right) compared with that in an HC (left). (G) Percentages of total hematogones (stages 1-3), (H) stage 1 hematogones (CD19+CD45dim), and (I) stage 2 hematogones (CD19+CD45intermediate) in the bone marrow from HC (n = 8), P-HLH (n = 6), I-HLH (n = 20), and R-HLH (n = 14) groups. Total: HC (n = 8) 12.70% ± 1.74%, P-HLH (n = 6) 6.74% ± 2.67%, I-HLH (n = 20) 4.78% ± 1.04%, and R-HLH (n = 14) 2.68% ± 0.65%; stage 1: HC 1.38% ± 0.13%, P-HLH 0.21% ± 0.12%, I-HLH 0.077% ± 0.035%, and R-HLH 0.019% ± 0.01%; stage 2: HC 8.38% ± 1.28%, P-HLH 0.79% ± 0.46%, I-HLH 0.27% ± 0.11%, and R-HLH 0.16% ± 0.05%. (J) Percentages of immature B cells (CD19+CD10+), (K) transitional B cells (CD19+CD10−CD20−), and (L) mature B cells (CD19+CD10−CD20+) in the bone marrow of patients in each group. Immature: HC (n = 8; 8.36% ± 1.06%), P-HLH (n = 6; 1.32% ± 0.65%), I-HLH (n = 19; 0.54% ± 0.15%), and R-HLH (n = 14; 0.20% ± 0.05%); transitional: HC 2.91% ± 0.38%, P-HLH 8.33% ± 3.12%, I-HLH 5.97% ± 1.09%, and R-HLH 3.02% ± 0.60%; and mature: HC 2.35% ± 0.42%, P-HLH 2.72% ± 1.01%, I-HLH 4.52% ± 1.13%, and R-HLH 1.77% ± 0.42%. The two-tailed Student t test or the Mann-Whitney test was used depending on normality for statistical comparison between 2 groups. The Kruskal-Wallis 1-way analysis of variance (ANOVA) followed by the Dunn multiple comparison test for non-normally distributed samples and an ordinary 1-way ANOVA followed by the Tukey multiple comparison test for normally distributed samples were used for statistical comparison of HC and HLH groups. Data represent mean ± standard error of the mean (SEM); ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001; ns, not significant.

Early B-cell development is suppressed in the bone marrows of patients with HLH. (A) The individual percentages of CD19+ (B-cell lineage), CD3+ (T-cell lineage), and CD33+ (myeloid lineage) cells in the bone marrow compartment for age-matched healthy control (HC) group (n = 8), P-HLH group (n = 5), I-HLH group (n = 19), and R-HLH group (n = 12). B-cell compartment (HC, 16.59% ± 1.85%; P-HLH, 10.78% ± 4.05%; I-HLH, 6.04% ± 1.19%; and R-HLH, 3.64% ± 0.76%); T-cell compartment (HC, 11.16% ± 1.01%; P-HLH, 28.38% ± 4.36%; I-HLH, 18.21% ± 2.48%; and R-HLH, 14.78% ± 3.36%); myeloid compartment (HC, 4.20% ± 0.62%; P-HLH, 8.93% ± 1.84%; I-HLH, 8.02% ± 1.09%; and R-HLH, 5.95% ± 1.07%). (B) Percentage of hematopoietic stem and progenitor cells (CD34+CD38−) population in the bone marrow compared among HC (n = 8; 0.17% ± 0.06%), P-HLH (n = 3; 0.055% ± 0.04%), I-HLH (n = 4; 0.024% ± 0.005%), and R-HLH (n = 4; 0.096% ± 0.04%). (C) Percentage of HPC (CD34+CD38+) population in the bone marrow compared among HC (n = 8; 2.94% ± 0.19%), P-HLH (n = 3; 1.87% ± 0.63%), I-HLH (n = 4; 1.90% ± 0.48%), and R-HLH (n = 4; 0.90% ± 0.49%) groups. (D) Percentages of pre–pro-B cells (CD34+CD19−CD10+) in HC (n = 8; 0.12% ± 0.03%) and HLH (n = 7; 0.0047% ± 0.0020%) groups and (E) pro-B cells (CD34+CD19+CD10+) in in the bone marrow of HC (n = 8; 1.26% ± 0.13%) and HLH (n = 7; 0.023% ± 0.017%) groups. (F) Representative flow cytometry dot plot of CD19/CD45 showing the depletion of hematogones (CD19+CD45+) in a patient with P-HLH (right) compared with that in an HC (left). (G) Percentages of total hematogones (stages 1-3), (H) stage 1 hematogones (CD19+CD45dim), and (I) stage 2 hematogones (CD19+CD45intermediate) in the bone marrow from HC (n = 8), P-HLH (n = 6), I-HLH (n = 20), and R-HLH (n = 14) groups. Total: HC (n = 8) 12.70% ± 1.74%, P-HLH (n = 6) 6.74% ± 2.67%, I-HLH (n = 20) 4.78% ± 1.04%, and R-HLH (n = 14) 2.68% ± 0.65%; stage 1: HC 1.38% ± 0.13%, P-HLH 0.21% ± 0.12%, I-HLH 0.077% ± 0.035%, and R-HLH 0.019% ± 0.01%; stage 2: HC 8.38% ± 1.28%, P-HLH 0.79% ± 0.46%, I-HLH 0.27% ± 0.11%, and R-HLH 0.16% ± 0.05%. (J) Percentages of immature B cells (CD19+CD10+), (K) transitional B cells (CD19+CD10−CD20−), and (L) mature B cells (CD19+CD10−CD20+) in the bone marrow of patients in each group. Immature: HC (n = 8; 8.36% ± 1.06%), P-HLH (n = 6; 1.32% ± 0.65%), I-HLH (n = 19; 0.54% ± 0.15%), and R-HLH (n = 14; 0.20% ± 0.05%); transitional: HC 2.91% ± 0.38%, P-HLH 8.33% ± 3.12%, I-HLH 5.97% ± 1.09%, and R-HLH 3.02% ± 0.60%; and mature: HC 2.35% ± 0.42%, P-HLH 2.72% ± 1.01%, I-HLH 4.52% ± 1.13%, and R-HLH 1.77% ± 0.42%. The two-tailed Student t test or the Mann-Whitney test was used depending on normality for statistical comparison between 2 groups. The Kruskal-Wallis 1-way analysis of variance (ANOVA) followed by the Dunn multiple comparison test for non-normally distributed samples and an ordinary 1-way ANOVA followed by the Tukey multiple comparison test for normally distributed samples were used for statistical comparison of HC and HLH groups. Data represent mean ± standard error of the mean (SEM); ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001; ns, not significant.

Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal