Low expression of CD200 predicts shorter time-to-treatment in chronic lymphocytic leukemia

Abstract

CD200, formerly known as OX-2, is a type I glycoprotein that is expressed on a variety of cell types. CD200 has been shown to be overexpressed in chronic lymphocytic leukemia (CLL). Although previous studies have confirmed the diagnostic value of CD200 in differentiating CLL from to other B-cell chronic lymphoproliferative disorders especially mantle cell lymphoma, whether CD200 has prognostic significance in CLL remains to be determined. We evaluated the mean fluorescence intensity (MFI) of CD200 in 307 consecutive, untreated patients with CLL in our center using flow cytometry. Using a CD200 MFI cutoff of 189.5, these cases could be divided into two groups. Patients with lower CD200 MFI (< 189.5) had a significantly shorter time-to-treatment (TTT) than those with higher CD200 MFI (≥ 189.5) (median TTT: 2 months vs 28 months, p = 0.0008). However, the effect of CD200 MFI on overall survival was not significant (CD200 MFI < 189.5: undefined vs CD200 MFI ≥ 189.5: undefined, P = 0.2379). In subgroup analysis, CD200 MFI retained its prognostic value in patients with favourable characteristics such as Binet stage A disease, mutated IGHV status, normal TP53 or negative CD38 expression. In conclusion, our study identified CD200 MFI as a potential prognostic factor in CLL.

Keywords: CD200; chronic lymphocytic leukemia; mean fluorescence intensity; prognosis; time to treatment.

Figure 1. Gating information (A) and representative data plots of CD200 positive (B) and negative (C) cases

Figure 2. CD200 MFI of CD19+CD200+ cells in CLL cases, the red line indicated the median CD200 MFI

Figure 3. Kaplan-Meier curves of TTT and survival based on CD200 expression (positive versus negative)

There was no significant difference between CD200 positive cases and negative cases in OS (A) and TTT (B).

Figure 4. Kaplan-Meier curves of TTT and survival based on CD200 MFI

CD200 MFI < 189.5 was predictive of reduced TTT (A), by using median CD200 MFI 192.6 as cutoff, the median TTT for patients with low CD200 MFI and high CD200 MFI were 2 months and 33 months, respectively (B), while using mean CD200 MFI 235.8 as cutoff, the median TTT for patients with low CD200 MFI and high CD200 MFI were 4 months and 28 months, respectively (C), CD200 MFI < 189.5 was not predictive of reduced survival (D).

Figure 5. CD200 MFI < 189.5 was also predictive of shorter TTT in 235 patients with PB specimens (A) and 72 patients with BM specimens (B)

Figure 6. Changes in CD200 MFI during progression in 11 cases

Figure 7. CD200 MFI < 189.5 refined TTT classified by Binet stage (A), IGHV status (B), TP53 status (C) and CD38 expression (D)

Figure 8. CD200 MFI < 189.5 predicted shorted TTT in patients with Binet A/B diseases (A), and also improved prognostification by IGHV status (B), TP53 status (C), and CD38 expression (D)

Figure 9. CD200 MFI < 189.5 indentified patients with relatively rapid progression in 70 patients in Binet A/B stage without any classical unfavorable prognostic factor (TP53 aberration, unmuated IGHV status, or CD38 expression)