![]() This history raises the potential for both genetic and environmental factors contributing to the development of CML in these 2 patients. In the case presented here, the family had a significant exposure history to genotoxic chemicals in earlier generations as well as a compelling history of cancer. The rarity of this disease argues against, but does not exclude, coincidental cases of CML in the same family. Indeed, fewer than 8,500 cases of CML are estimated to occur in the USA in 2020. Most of these reported cases have been described in first-degree relatives, leaving minimal information on cases described in more distantly related individuals. In a systematic review of chronic myeloproliferative neoplasms occurring in families, almost 10% of cases involved CML. CML is not generally considered to harbor a familial pattern although rare cases of possible familial CML have been described (Table 1). We have described an instance of third-degree relatives sharing a CML diagnosis. Patient remains well and will continue to follow in our clinic every 2 months with PCR monitoring. After approximately 2 months of bosutinib treatment, PB PCR had decreased to 0.4%. After 3 months at this higher dasatinib dose, PCR continued to increase, reaching 8.84% in bone marrow, at which time treatment was switched to bosutinib 400 mg daily. ![]() Given the lack of ABL1 kinase domain mutations, dasatinib was increased to 100 mg per day. Approximately 2.5 years after initial diagnosis, PB PCR began to trend upward, at which time ABL1 was sequenced and no kinase domain mutations were detected. As she was in a deep molecular remission at the time of sequencing, no somatic mutations were detected, though 2 variants of probable germline origin were identified in KDM6A 2177C>A (T726K) and TET2 1088C>T (P363L). Due to this new family history of hematologic malignancy, a targeted next-generation sequencing-based 81-gene panel was performed on bone marrow at this time to evaluate for any germline mutations that could underlie a putative genetic predisposition to CML. At a follow-up visit, the patient disclosed that her maternal great aunt had recently received a CML diagnosis.
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