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Transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha) is mutated in 6-10% of patients with acute myeloid leukaemia (AML). Recently, we reported the emergence of an N-terminal C/EBPalpha mutation after chemotherapy in a patient with secondary AML. The clone carrying the mutation became the dominant clone at relapse. This observation prompted us to compare the C/EBPalpha mutational status of 26 de novo non-core binding factor AML patients at diagnosis and at relapse after induction and consolidation chemotherapy. Four mutations in the C/EBPalpha gene were identified in two out of 26 patients. In both these cases, a biallelic mutation was present at diagnosis and at relapse: an amino-terminal frameshift mutation and a mutation of the fork/leucine finger 1 region. In patient 1, the amino-terminal frameshift mutation was duplicated and found on both alleles at relapse. In patient 2, the amino-terminal frameshift mutation and a mutation in the fork region were found either alone or combined on the same allele, suggesting a subclone formation. None of the patients without a C/EBPalpha mutation at diagnosis showed a mutation at relapse. This is the first report of an evolution of the C/EBPalpha gene between diagnosis and relapse in AML.

Transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha) is mutated in 6-10% of patients with acute myeloid leukaemia (AML). Recently, we reported the emergence of an N-terminal C/EBPalpha mutation after chemotherapy in a patient with secondary AML. The clone carrying the mutation became the dominant clone at relapse. This observation prompted us to compare the C/EBPalpha mutational status of 26 de novo non-core binding factor AML patients at diagnosis and at relapse after induction and consolidation chemotherapy. Four mutations in the C/EBPalpha gene were identified in two out of 26 patients. In both these cases, a biallelic mutation was present at diagnosis and at relapse: an amino-terminal frameshift mutation and a mutation of the fork/leucine finger 1 region. In patient 1, the amino-terminal frameshift mutation was duplicated and found on both alleles at relapse. In patient 2, the amino-terminal frameshift mutation and a mutation in the fork region were found either alone or combined on the same allele, suggesting a subclone formation. None of the patients without a C/EBPalpha mutation at diagnosis showed a mutation at relapse. This is the first report of an evolution of the C/EBPalpha gene between diagnosis and relapse in AML.

Tumour cells from a patient with recurrent testicular germ cell cancer and bone marrow infiltration were found to express CD33 and CD34 in the absence of other haemopoiesis-associated antigens. After myelosuppression and treatment with G-CSF for stem cell mobilization, CD34-positive tumour cells were detected in the peripheral blood in addition to normal haemopoietic progenitor cells. The tumour cells were decreased in the leukapheresis product. Retrospectively, the appearance of tumour cells in the peripheral blood after stem cell mobilization was the first indication of impending relapse.