Figure 2.
Spontaneously regressed CLL tumors are composed of a nonproliferating CLL clone that has previously undergone substantial cell division. (A) A CD19 gate was applied to the peripheral blood mononuclear cells (PBMCs) to select for CD19+ B lymphocytes (not shown). The CLL population (shown in red) could be distinguished from the nonmalignant B-lymphocyte population (shown in green) by their immunophenotype, as demonstrated by the example of CLL05. CLL cells exhibit high CD5 and CD43 but low CD20, CD79b, and CD81 expression, whereas nonmalignant B lymphocytes exhibit high CD20, CD79b, and/or CD81 expression. This methodology was used to determine the proportion of CLL cells within the B-lymphocyte population, the results of which are displayed in Table 2. (B-C) The gated CLL population of PBMCs was analyzed for the expression of Ki-67 and CXCR4. For each comparison, 17 spontaneous regression cases (REG) from the regression time point (T1) were compared against 54 indolent (INDOL) and 40 progressive (PROG) cases. Complete and partial spontaneous regression cases are represented by red and blue dots, respectively, as shown. Statistical significance was determined using 1-way analysis of variance (ANOVA) with Bonferroni post hoc analysis for cohort comparison and the 2-tailed paired Student t test for time point comparison. Statistical significance is indicated by *P < .05, **P < .01, and ****P < .0001. (D) Expression of Ki-67 and CXCR4 was compared between 2 sequential time points in individual spontaneous regression cases. T0 and T1 represent the diagnostic and the regression time point, respectively. Each colored line represents a specific case as indicated. (E) XpYp single-telomere length analysis was performed on sorted CD19+CD5+ CLLs to assess the telomere length of chromosomes Xp and Yp of CLL cells. Left panel, The telomere length distribution of the CD19+CD5+ sorted CLL Xp and Yp chromosomes in each case. Right panel, The mean CLL XpYp telomere length was compared between spontaneously regressed and indolent cases. Complete and partial spontaneous regression cases are represented by red and blue dots, respectively, as shown. Statistical significance was determined using the Student t test. ns, comparisons that are not statistically significant.

Spontaneously regressed CLL tumors are composed of a nonproliferating CLL clone that has previously undergone substantial cell division. (A) A CD19 gate was applied to the peripheral blood mononuclear cells (PBMCs) to select for CD19+ B lymphocytes (not shown). The CLL population (shown in red) could be distinguished from the nonmalignant B-lymphocyte population (shown in green) by their immunophenotype, as demonstrated by the example of CLL05. CLL cells exhibit high CD5 and CD43 but low CD20, CD79b, and CD81 expression, whereas nonmalignant B lymphocytes exhibit high CD20, CD79b, and/or CD81 expression. This methodology was used to determine the proportion of CLL cells within the B-lymphocyte population, the results of which are displayed in Table 2. (B-C) The gated CLL population of PBMCs was analyzed for the expression of Ki-67 and CXCR4. For each comparison, 17 spontaneous regression cases (REG) from the regression time point (T1) were compared against 54 indolent (INDOL) and 40 progressive (PROG) cases. Complete and partial spontaneous regression cases are represented by red and blue dots, respectively, as shown. Statistical significance was determined using 1-way analysis of variance (ANOVA) with Bonferroni post hoc analysis for cohort comparison and the 2-tailed paired Student t test for time point comparison. Statistical significance is indicated by *P < .05, **P < .01, and ****P < .0001. (D) Expression of Ki-67 and CXCR4 was compared between 2 sequential time points in individual spontaneous regression cases. T0 and T1 represent the diagnostic and the regression time point, respectively. Each colored line represents a specific case as indicated. (E) XpYp single-telomere length analysis was performed on sorted CD19+CD5+ CLLs to assess the telomere length of chromosomes Xp and Yp of CLL cells. Left panel, The telomere length distribution of the CD19+CD5+ sorted CLL Xp and Yp chromosomes in each case. Right panel, The mean CLL XpYp telomere length was compared between spontaneously regressed and indolent cases. Complete and partial spontaneous regression cases are represented by red and blue dots, respectively, as shown. Statistical significance was determined using the Student t test. ns, comparisons that are not statistically significant.

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