Intra-tumoralgenetic heterogeneity and number of cytogenetic aberrations provideadditional prognostic significance in chronic lymphocytic leukemia

Supplementary

Figure S1

The survival comparison between patients without cytogenetic aberration and with sole del 13q

Figure S2

The survival comparison between patients with del 11q but without del 17p and patients with del 17p

Figure S3

The representative images of the intra-tumoral clones

A: One case with 82% deletion of 11q (red signal) and 30% deletion of 13q (green signal); a, cell with both deletion of 11q and 13q (minor clone); b cells with deletion of 11q and normal 13q (major clone). This case meets the definition of unfavorable clone as major.

B: One case with 75% trisomy 12 (red signal) and 36% deletion of 17p (green signal); c, normal cell with two red and green signals; d, cell with trisomy 12 and deletion of 17p (minor clone); e, cells with trisomy 12 and normal 17p (major clone). This case meets the definition of unfavorable clone

Figure S4

The survival comparison within patients with different cytogenetic aberration numbers

Figure S5

Within the conventional cytogenetic favorable group, patients with concomitant del 13q, trisomy 12 and t(14q32) had a poorer survival rate compared with patients harboring one or two of the aberrations (A,B and C). While within the conventional cytogenetic unfavorable group, patients with a unfavorable clone as the minor clone had a significant survival advantage compared with other patients with a poor clone (E,F and G).

Figure S6

The survival comparison within patients with one or two intratumoral favorablecytogenetic subclones

Figure S7

Concomitant with del 13q, trisomy 12 and t(14q32) had significantly worsen overall survival in favorable group patients but without sole del 13q.

Table S1. Survival comparison between all negative and sole del 13q or between del 11q without del 17p and del 17p

Cytogenetic aberration / N / TTT / P / PFS / P / OS / P
Favorable group / .056 / .084 / .289
All negative / 70 / 23.5(6.1-40.9) / 107.0(not estimated) / Not reached
Sole del 13q / 77 / 49.0(27.2-70.8) / 193.0(72.2-313.8) / Not reached
Unfavorable group / .449 / .102 / .149
Del 11q without del 17p / 37 / 12.5(6.6-18.4) / 60.0(38.9-81.1) / 94.0(not estimated)
Del 17p / 46 / 12.5(0-25.3) / 35.0(18.2-51.8) / 78.0(57.3-98.7)

Table S2. The survival comparison between different re-classified cytogenetic subgroups

Re-classified cytogenetic subgroups / N / TTT / P / PFS / P / OS / P
.414 / .840 / .408
Unfavorable clone as minor / 13 / 31.0(3.4-58.6) / Not reached / Not reached
Trisomy 12 and/or t(14q32) and/or del 13q with less than 3 aberrations / 91 / 25.5(13.1-37.9) / 92.0(78.9-105.1) / 162.0(89.3-234.7)
All negative or sole del 13q / 147 / 36.0(23.0-49.0) / 193.0(72.2-313.8) / Not reached
.567 / .587 / .904
Concomitant trisomy 12,t(14q32) and del13q / 5 / 25.0(5.9-44.1) / 45.0(32.1-57.9) / 88.0(20.9-155.1)
One unfavorable clone or unfavorable clone as major / 70 / 12.0(6.5-17.5) / 37.0(16.2-57.8) / 74.0(58.4-89.6)

Table S3.Patients with Del 13q plus trisomy 12 had similar survival compared to patients with sole trisomy 12.

Cytogenetic aberration / N / TTT / P / PFS / P / OS / P
.432 / .404 / .322
Del 13q+trisomy 12 / 12 / 21.0(0-84.7) / 113.5(85.9-141.1) / 131.0(104.4-157.6)
Sole trisomy 12 / 30 / 24.0(11.2-36.8) / 70.0(42.3-97.7) / 100.0(83.8-116.2)