Clonal heterogeneity in patients with cytogenetically normal acute myeloid leukemia with NPM1 mutations

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Authors

DVOŘÁKOVÁ Dana RÁČIL Zdeněk BORSKÝ Michal ROBEŠOVÁ Blanka JEŽÍŠKOVÁ Ivana RÁZGA Filip LENGEROVÁ Martina MAYER Jiří

Year of publication 2013
Type Article in Periodical
Magazine / Source Leukemia & Lymphoma
MU Faculty or unit

Central European Institute of Technology

Citation
Web http://informahealthcare.com/doi/abs/10.3109/10428194.2012.734618
Doi http://dx.doi.org/10.3109/10428194.2012.734618
Field Oncology and hematology
Keywords AML; NPM1; lymphoid lineages; HSC
Attached files
Description The nucleophosmin 1 (NPM1) gene is one of the most commonly mutated genes in acute myeloid leukemia (AML), occurring in approximately 60% of adult cytogenetically normal AML (CN-AML). To date, these mutations have only been detected in cells of the myeloid lineage, whereas the potential clonal involvement of the lymphoid lineage is controversial. In our study, NPM1 mutations were analyzed using the highly sensitive real-time quantitative polymerase chain reaction (RQ-PCR) method on fluorescence-activated cell-sorted (FACS) purified different circulating mature cell populations in patients with NPM1-mutated CN-AML. As expected, NPM1 mutations were found in myeloid blood cells, including CD14(+) monocytes and CD66b(+) granulocytes. However, we were also able to detect NPM1 mutations in CD19(+) B cells and CD3(-)14(-)16(+)56(+) natural killer (NK) cells, albeit at lower levels. Surprisingly, mutations were also detected in CD3(+) T cells from all analyzed patients. Our data demonstrate that NPM1-mutated CN-AML originates in an early stem cell with both lymphoid and myeloid differentiation potential.
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