Novel gene targets detected by genomic profiling in a consecutive series of 126 adults with acute lymphoblastic leukemia

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Novel gene targets detected by genomic profiling in a consecutive series of 126 adults with acute lymphoblastic leukemia. / Safavi, Setareh; Hansson, Markus; Karlsson, Karin; Biloglav, Andrea; Johansson, Bertil; Paulsson, Kajsa.

I: Haematologica, Vol. 100, Nr. 1, 2015, s. 55-61.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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Safavi, Setareh ; Hansson, Markus ; Karlsson, Karin ; Biloglav, Andrea ; Johansson, Bertil ; Paulsson, Kajsa. / Novel gene targets detected by genomic profiling in a consecutive series of 126 adults with acute lymphoblastic leukemia. I: Haematologica. 2015 ; Vol. 100, Nr. 1. s. 55-61.

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TY - JOUR

T1 - Novel gene targets detected by genomic profiling in a consecutive series of 126 adults with acute lymphoblastic leukemia

AU - Safavi, Setareh

AU - Hansson, Markus

AU - Karlsson, Karin

AU - Biloglav, Andrea

AU - Johansson, Bertil

AU - Paulsson, Kajsa

PY - 2015

Y1 - 2015

N2 - In contrast to acute lymphoblastic leukemia in children, adult cases of this disease are associated with a very poor prognosis. In order to ascertain whether the frequencies and patterns of submicroscopic changes, identifiable with single nucleotide polymorphism array analysis, differ between childhood and adult acute lymphoblastic leukemia, we performed single nucleotide polymorphism array analyses of 126 adult cases, the largest series to date, including 18 paired diagnostic and relapse samples. Apart from identifying characteristic microdeletions of the CDKN2A, EBF1, ETV6, IKZF1, PAX5 and RB1 genes, the present study uncovered novel, focal deletions of the BCAT1, BTLA, NR3C1, PIK3AP1 and SERP2 genes in 2-6% of the adult cases. IKZF1 deletions were associated with B-cell precursor acute lymphoblastic leukemia (P=0.036), BCR-ABL1-positive acute lymphoblastic leukemia (P<0.001), and higher white blood cell counts (P=0.005). In addition, recurrent deletions of RASSF3 and TOX were seen in relapse samples. Comparing paired diagnostic/relapse samples revealed identical changes at diagnosis and relapse in 27%, clonal evolution in 22%, and relapses evolving from ancestral clones in 50%, akin to what has previously been reported in pediatric acute lymphoblastic leukemia and indicating that the mechanisms of relapse may be similar in adult and childhood cases. These findings provide novel insights into the leukemogenesis of adult acute lymphoblastic leukemia, showing similarities to childhood disease in the pattern of deletions and the clonal relationship between diagnostic and relapse samples, but with the adult cases harboring additional aberrations that have not been described in pediatric acute lymphoblastic leukemia.

AB - In contrast to acute lymphoblastic leukemia in children, adult cases of this disease are associated with a very poor prognosis. In order to ascertain whether the frequencies and patterns of submicroscopic changes, identifiable with single nucleotide polymorphism array analysis, differ between childhood and adult acute lymphoblastic leukemia, we performed single nucleotide polymorphism array analyses of 126 adult cases, the largest series to date, including 18 paired diagnostic and relapse samples. Apart from identifying characteristic microdeletions of the CDKN2A, EBF1, ETV6, IKZF1, PAX5 and RB1 genes, the present study uncovered novel, focal deletions of the BCAT1, BTLA, NR3C1, PIK3AP1 and SERP2 genes in 2-6% of the adult cases. IKZF1 deletions were associated with B-cell precursor acute lymphoblastic leukemia (P=0.036), BCR-ABL1-positive acute lymphoblastic leukemia (P<0.001), and higher white blood cell counts (P=0.005). In addition, recurrent deletions of RASSF3 and TOX were seen in relapse samples. Comparing paired diagnostic/relapse samples revealed identical changes at diagnosis and relapse in 27%, clonal evolution in 22%, and relapses evolving from ancestral clones in 50%, akin to what has previously been reported in pediatric acute lymphoblastic leukemia and indicating that the mechanisms of relapse may be similar in adult and childhood cases. These findings provide novel insights into the leukemogenesis of adult acute lymphoblastic leukemia, showing similarities to childhood disease in the pattern of deletions and the clonal relationship between diagnostic and relapse samples, but with the adult cases harboring additional aberrations that have not been described in pediatric acute lymphoblastic leukemia.

U2 - 10.3324/haematol.2014.112912

DO - 10.3324/haematol.2014.112912

M3 - Article

VL - 100

SP - 55

EP - 61

JO - Haematologica-The Hematology Journal

T2 - Haematologica-The Hematology Journal

JF - Haematologica-The Hematology Journal

SN - 1592-8721

IS - 1

ER -