Archived cytogenetic cell pellets used to detect a BCR::ABL1 driver mutation eight years before disease presentation: a case report

Abstract

Abstract Background: Evidence suggests that the earliest genetic events in the evolution of a cancer can predate diagnosis by several years or decades. In chronic myeloid leukemia (CML), the BCR::ABL1 fusion driver mutation can be present for an extended period before clinical disease manifests. The time between the BCR::ABL1 occurrence and symptom onset is referred to as the latency period. Though modeling studies predict this latency period is no more than ten years, it is still unclear how long it can be. Case presentation: A 57-year-old female patient with anemia, fatigue, weight loss and night sweating was referred for suspected CML. Both karyotype and FISH analysis identified the t(9;22)(q34;q11.2) translocation resulting in the Philadelphia chromosome formation. The patient responded to imatinib and achieved a sustained complete hematologic and cytogenetic remission. Clinical history revealed that this patient was evaluated eight years previous for mild anemia and cytopenia with suspicion of myelodysplastic syndrome (MDS). There was macrocytic anemia and mild polychromasia on the peripheral blood smear which was remarkable for mild leukocytosis without a left-shift or circulating blasts. The bone marrow was normocellular without significant dysplasia and no evidence of a myeloid neoplasm. Cytogenetic analysis at that time revealed del(20q) as the sole abnormality. The patient’s condition resolved, and no treatment was provided because isolated del(20q) is not considered evidence of MDS in the absence diagnostic morphologic findings. Cytogenetic fluorescent in situ hybridization analysis of the eight-year-old archived bone marrow pellets revealed the presence of BCR::ABL1 fusion in 1.8% of cells. Conclusion: A clonal population of cells harboring the BCR::ABL1 fusion was unambiguously detected in this patient’s archived bone marrow pellet obtained eight years before the current CML diagnosis. This case demonstrates that Carnoy’s fixed nuclear pellets stored in cytogenetic laboratories are suitable for detecting driver mutations years before disease presentation. Such archived material may be useful for the retrospective studies needed to better understand the initiation and subsequent development of hematological malignancies. By identifying individuals who are at increased risk, it may be possible to initiate preventive measures or begin treatment at an earlier stage before disease progression