TY - JOUR
T1 - Complex karyotype in de novo acute myeloid leukemia
T2 - typical and atypical subtypes differ molecularly and clinically
AU - Mrózek, Krzysztof
AU - Eisfeld, Ann Kathrin
AU - Kohlschmidt, Jessica
AU - Carroll, Andrew J.
AU - Walker, Christopher J.
AU - Nicolet, Deedra
AU - Blachly, James S.
AU - Bill, Marius
AU - Papaioannou, Dimitrios
AU - Wang, Eunice S.
AU - Uy, Geoffrey L.
AU - Kolitz, Jonathan E.
AU - Powell, Bayard L.
AU - Blum, William
AU - Stone, Richard M.
AU - Byrd, John C.
AU - Bloomfield, Clara D.
N1 - Publisher Copyright:
© 2019, Springer Nature Limited.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Complex karyotype (CK) with ≥ 3 abnormalities is detected in 10–12% of patients with acute myeloid leukemia (AML) and associated with poor prognosis. The most common unbalanced abnormalities found in CK result in loss of material from the 5q, 7q, and/or 17p chromosome arms. The presence of 5q, 7q, and/or 17p abnormalities denotes typical CK and their absence denotes atypical CK. Since molecular features of CK-AML are not well characterized, we investigated mutational status of 81 leukemia/cancer-associated genes in 160 clinically well-characterized patients. They included 136 patients with ≥ 3 exclusively unbalanced chromosome abnormalities, 96 of whom had a typical CK and 40 atypical CK, and 24 patients with ≥ 1 balanced abnormality in addition to ≥ 2 unbalanced ones. Patients with atypical CK-AML differed from those with typical CK-AML: they carried TP53 mutations less often (P < 0.001) and more often PHF6 (P = 0.008), FLT3-TKD (P = 0.02), MED12 (P = 0.02), and NPM1 (P = 0.02) mutations. They were younger (P = 0.007), had higher WBC (P = 0.001) and percentages of marrow (P < 0.001) and blood (P = 0.006) blasts, higher complete remission rates (P = 0.02), and longer overall survival (P < 0.001), thus indicating that atypical and typical CK-AMLs constitute distinct disease subtypes. We also identified smaller patient subsets within both typical and atypical CK-AML that differed molecularly and clinically.
AB - Complex karyotype (CK) with ≥ 3 abnormalities is detected in 10–12% of patients with acute myeloid leukemia (AML) and associated with poor prognosis. The most common unbalanced abnormalities found in CK result in loss of material from the 5q, 7q, and/or 17p chromosome arms. The presence of 5q, 7q, and/or 17p abnormalities denotes typical CK and their absence denotes atypical CK. Since molecular features of CK-AML are not well characterized, we investigated mutational status of 81 leukemia/cancer-associated genes in 160 clinically well-characterized patients. They included 136 patients with ≥ 3 exclusively unbalanced chromosome abnormalities, 96 of whom had a typical CK and 40 atypical CK, and 24 patients with ≥ 1 balanced abnormality in addition to ≥ 2 unbalanced ones. Patients with atypical CK-AML differed from those with typical CK-AML: they carried TP53 mutations less often (P < 0.001) and more often PHF6 (P = 0.008), FLT3-TKD (P = 0.02), MED12 (P = 0.02), and NPM1 (P = 0.02) mutations. They were younger (P = 0.007), had higher WBC (P = 0.001) and percentages of marrow (P < 0.001) and blood (P = 0.006) blasts, higher complete remission rates (P = 0.02), and longer overall survival (P < 0.001), thus indicating that atypical and typical CK-AMLs constitute distinct disease subtypes. We also identified smaller patient subsets within both typical and atypical CK-AML that differed molecularly and clinically.
UR - http://www.scopus.com/inward/record.url?scp=85061304550&partnerID=8YFLogxK
U2 - 10.1038/s41375-019-0390-3
DO - 10.1038/s41375-019-0390-3
M3 - Article
C2 - 30737482
AN - SCOPUS:85061304550
SN - 0887-6924
VL - 33
SP - 1620
EP - 1634
JO - Leukemia
JF - Leukemia
IS - 7
ER -