Patients with chronic lymphocytic leukaemia and clonal deletion of both 17p13.1 and 11q22.3 have a very poor prognosis

Patricia T. Greipp, Stephanie A. Smoley, David S. Viswanatha, Lori S. Frederick, Kari G. Rabe, Ruchi G. Sharma, Susan L. Slager, Daniel L. Van Dyke, Tait D. Shanafelt, Renee C. Tschumper, Clive S. Zent

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Detection of a 17p13.1 deletion (loss of TP53) or 11q22.3 deletion (loss of ATM), by fluorescence in situ hybridization (FISH), in chronic lymphocytic leukaemia (CLL) patients is associated with a poorer prognosis. Because TP53 and ATM are integral to the TP53 pathway, we hypothesized that 17p13.1- (17p-) and 11q22.3- (11q-) occurring in the same cell (clonal 17p-/11q-) would confer a worse prognosis than either 17p- or 11q- We studied 2184 CLL patients with FISH (1995-2012) for the first occurrence of 17p-, 11q-, or clonal 17p-/11q- Twenty (1%) patients had clonal 17p-/11q-, 158 (7%) had 17p- (including 4 with 17p- and 11q- in separate clones), 247 (11%) had 11q-, and 1759 (81%) had neither 17p- nor 11q- Eleven of 15 (73%) tested patients with clonal 17p-/11q- had dysfunctional TP53 mutations. Overall survival for clonal 17p-/11q- was significantly shorter (1·9 years) than 17p- (3·1 years, P = 0·04), 11q- (4·8 years, P ≤ 0·0001), or neither 17p- nor 11q- (9·3 years, P ≤ 0·0001). Clonal 17p-/11q- thus conferred significantly worse prognosis, suggesting that loss of at least one copy of both TP53 and ATM causes more aggressive disease. Use of an ATM/TP53 combination FISH probe set could identify these very-high risk patients.

Original languageEnglish (US)
Pages (from-to)326-333
Number of pages8
JournalBritish journal of haematology
Volume163
Issue number3
DOIs
StatePublished - Nov 2013

Keywords

  • ATM
  • Chronic lymphocytic leukaemia
  • Fluorescence in situ hybridization (FISH)
  • Prognostic factors
  • TP53

ASJC Scopus subject areas

  • Hematology

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    Greipp, P. T., Smoley, S. A., Viswanatha, D. S., Frederick, L. S., Rabe, K. G., Sharma, R. G., Slager, S. L., Van Dyke, D. L., Shanafelt, T. D., Tschumper, R. C., & Zent, C. S. (2013). Patients with chronic lymphocytic leukaemia and clonal deletion of both 17p13.1 and 11q22.3 have a very poor prognosis. British journal of haematology, 163(3), 326-333. https://doi.org/10.1111/bjh.12534