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Patients with chronic lymphocytic leukaemia and clonal deletion of both 17p13.1 and 11q22.3 have a very poor prognosis
Author(s) -
Greipp Patricia T.,
Smoley Stephanie A.,
Viswanatha David S.,
Frederick Lori S.,
Rabe Kari G.,
Sharma Ruchi G.,
Slager Susan L.,
Van Dyke Daniel L.,
Shanafelt Tait D.,
Tschumper Renee C.,
Zent Clive S.
Publication year - 2013
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12534
Subject(s) - fluorescence in situ hybridization , somatic evolution in cancer , biology , medicine , chromosome , oncology , cancer research , gene , genetics
Summary Detection of a 17p13.1 deletion (loss of TP 53 ) 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 TP 53 and ATM are integral to the TP 53 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 TP 53 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 TP 53 and ATM causes more aggressive disease. Use of an ATM / TP 53 combination FISH probe set could identify these very‐high risk patients.