BCR-ABL1(+) acute myeloid leukemia: clonal selection of a BCR-ABL1(-) subclone as a cause of refractory disease with nilotinib treatment.
The presence of a Philadelphia chromosome with a corresponding BCR-ABL1 rearrangement is the hallmark of chronic myeloid leukemia, but is considered a very rare event in de novo acute myeloid leukemia (AML). Here, we report the first case in which a dominant Philadelphia chromosome-positive subclone was detected upon relapse in a formerly Philadelphia chromosome-negative MLL-AF6(+) AML. Due to refractory disease under salvage chemotherapy, the patient was started on nilotinib treatment. As a result, the Philadelphia chromosome-positive subclone was eradicated within 1 month; however, disease progressed and was again dominated by the Philadelphia chromosome-negative founding clone, demonstrating rapid clonal expansion under nilotinib-induced selection pressure.
Department of Hematology, Oncology and Tumor Immunology, Charité-University Medicine Berlin, Berlin, Germany.
Nina Rosa
NR
Neuendorff
Michaela
M
Schwarz
Philipp
P
Hemmati
Seval
S
Türkmen
Christiane
C
Bommer
Thomas
T
Burmeister
Bernd
B
Dörken
Philipp
P
le Coutre
Renate
R
Arnold
Jörg
J
Westermann
D000368:Aged; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D010677:Philadelphia Chromosome; D011743:Pyrimidines / Q000008:administration & dosage*; D012008:Recurrence; D016879:Salvage Therapy / Q000379:methods
C581634:BCR-ABL1 fusion protein, human; D011743:Pyrimidines; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib