Fig. 1: MTCP1 is expressed in CLL patients and is associated with poor outcomes.

A Metaphase FISH was performed on CpG-stimulated CLL cells using the IGH break apart (3′red; 5′green) hybridization probes. Representative FISH analysis in one CLL patient harboring the t(X;14)(q28;q32) translocation showing the IGH probe has split with 5′ (green) on an X chromosome and 3′ (red) remaining on a chromosome 14. Images represent three independent tests. Scale bars are 10 µm. B Metaphase FISH was performed on CpG-stimulated CLL cells using the MTCP1 (red) hybridization probe. Representative FISH analysis in the patient from (A) showing the MTCP1 loci are on an X chromosome and on distal 14q. Images represent three independent tests. C Metaphase FISH was performed on CpG-stimulated CLL cells combining the IGH (3′red; 5′green) and MTCP1 (red) probes. Representative FISH analysis in the patient from (A) showing the MTCP1 and 3′IGH probes co-localize on a chromosome 14 and 5′(green) IGH is on an X chromosome. Images represent three independent tests. D MTCP1 mRNA expression is elevated in CLL cells (without any known Xq28 rearrangements) compared to naïve- or memory-B-cell subsets (p = 0.0012, p = 0.0013, respectively). Data obtained from the Blueprint database. Box elements reflect 2nd - 3rd quartile, center line reflects the median value, and whiskers reflect the distance from the upper and lower limit to the box elements. CLL cells – red/right, n = 7; naïve B cells – dark gray/left, n = 9; memory B cells – light gray/middle, n = 5. P value estimated using a two-tailed unpaired t test with Welch’s correction. E Higher MTCP1 expression in CLL patients identified with shorter progression-free survival (PFS) in chemoimmunotherapy trials. CLL patients from two independent study cohorts from Cancer and Leukemia Group B clinical trials (9712 and 10101; N = 103) were retrospectively analyzed. Patients were divided into quartiles: Q1 (solid line, n = 25), Q2 (medium-dash, n = 27), Q3 (short-dash, n = 26), and Q4 (long-dash, n = 25) according to MTCP1 expression and PFS was visualized using the Kaplan–Meier method. As a continuous variable, the crude hazard ratio for a 2-fold increase in expression is 1.86 (95% CI: 0.97–3.55, P = 0.06) estimated from a Cox proportional hazards model. P value was determined via two-sided Wald test. No adjustments were made for multiple testing.