bcr-abl融合蛋白，通常被称为费城染色体，是癌症中研究最多的融合基因之一。它被广泛认为是慢性粒细胞白血病（CML）的起始事件。然而，尽管它能够在小鼠体内引发疾病，但它作为一种起始突变的地位仍存在争议。伊马替尼在临床上的发展和使用，使该病的预后得到了极大的改善。然而，伊马替尼耐药仍见于融合的ABL激酶域突变患者，最显著的是T315I变异体。在对伊马替尼耐药的患者中，无论是获得性的还是其他的，第二代BCR-ABL-TKI（达沙替尼和尼洛替尼）在提供肿瘤应答方面取得了一些成功。第三代ABL1抑制剂ponatinib是FDA批准的唯一一种对T315I有活性的药物。然而，由于存在危及生命的血栓和严重的血管狭窄的风险，Ponatinib仅被批准用于T315I阳性CML或T315I阳性PH值+所有或CML、PH值+所有患者，并对其他经批准的ABL1抑制剂有耐药性或不耐受性。
The BCR-ABL fusion protein, commonly referred to as the Philadelphia chromosome, is one of the most studied fusion genes in cancer. It has widely been considered the initiating event in chronic myelogenous leukemia (CML). However, despite its ability to initiate disease in mice, its status as an initiating mutation is in dispute. In what is commonly used as the poster-child for targeted therapeutics, the development and use of imatinib in the clinic has led to profound improvements in the prognosis of the disease. However, imatinib resistance is still seen in patients with mutations in the ABL kinase domain of the fusion, most notably the T315I variant. In patients resistant to imatinib, either acquired or otherwise, second generation BCR-ABL TKI's (dasatinib and nilotinib) have seen some success in delivering a tumor response. Third generation ABL1 inhibitor ponatinib is the only FDA approved drug with activity against T315I . However due to risk of life-threatening blood clots and severe narrowing of blood vessels ponatinib is ONLY approved for T315I-positive CML or T315I-positive Ph+ ALL or in cases of CML, Ph+ ALL with resistance or intolerance to other approved ABL1 inhibitors.