The Novel Human Ph+ Acute Lymphoblastic Leukemia Cell Line PhALL3.1 Is Amenable to Retroviral Gene Transfer and Mimics Human Disease Progression in SCID-Beige Mice

Abstract Despite recent treatment advances, patients with Philadelphia (Ph) chromosome positive acute lymphoblastic leukemia (ALL) have a dismal prognosis. For this reason, a better understanding of the biology of Ph+ ALL, as well as novel approaches to treat this malignancy are needed. To date, there exist few primary Ph+ ALL tumor cell lines amenable to preclinical investigation of either the biology or treatment sensitivity of Ph+ ALL. In this report we describe the isolation and characterization of a novel Ph+ ALL cell line, designated PhALL3.1, obtained from a 62 year old patient who relapsed in the pleural space while receiving imatinib therapy. Tumor cells obtained from this malignant pleural effusion proliferated in standard complete RPMI media without supplementation with exogenous growth factors. The PhALL3.1 tumor expressed an unmutated p190 bcr-abl transcript, and demonstrated persistent sensitivity to both imatinib and desatinib in in vitro assays. Furthermore, we found that the PhALL3.1 cell line was readily amenable to retroviral gene transfer allowing for the modification of this line to express the green fluorescent protein-fire fly luciferase enzyme (PhALL3.1/GFP-FFL). When injected systemically into immune-compromised SCID-Beige mice, PhALL3.1/GFP-FFL tumor cells mimicked a clinical disease pattern with tumor involvement seen predominantly in the bone marrow, CNS, and spleen. This pattern of disease progression, as demonstrated by bioluminescent imaging, was further confirmed by histologic analysis. Likewise, when injected subcutaneously into immune-compromised mice, this cell line readily and reproducibly generated subcutaneous tumors. We conclude that the PhALL3.1 cell line is a novel, well characterized, cell line which readily proliferates both in vitro and in vivo, and therefore has significant value in future pre-clinical investigations into the biology of Ph+ ALL tumors as well as novel treatment approaches for this disease.