Profiling the B/T cell receptor repertoire of lymphocyte derived cell lines.

BACKGROUND: Clonal VDJ rearrangement of B/T cell receptors (B/TCRs) occurring during B/T lymphocyte development has been used as a marker to track the clonality of B/T cell populations. METHODS: We systematically profiled the B/T cell receptor repertoire of 936 cancer cell lines across a variety of cancer types as well as 462 Epstein-Barr Virus (EBV) transformed normal B lymphocyte lines using RNA sequencing data. RESULTS: Rearranged B/TCRs were readily detected in cell lines derived from lymphocytes, and subclonality or potential biclonality were found in a number of blood cancer cell lines. Clonal BCR/TCR rearrangements were detected in several blast phase CML lines and unexpectedly, one gastric cancer cell line (KE-97), reflecting a lymphoid origin of these cells. Notably, clonality was highly prevalent in EBV transformed B lymphocytes, suggesting either transformation only occurred in a few B cells or those with a growth advantage dominated the transformed population through clonal evolution. CONCLUSIONS: Our analysis reveals the complexity and heterogeneity of the BCR/TCR rearrangement repertoire and provides a unique insight into the clonality of lymphocyte derived cell lines.

Mutational profiling of acute lymphoblastic leukemia with testicular relapse.

Relapsed acute lymphoblastic leukemia (ALL) is the leading cause of deaths of childhood cancer. Although relapse usually happens in the bone marrow, extramedullary relapse occasionally occurs including either the central nervous system or testis (<1-2%). We selected two pediatric ALL patients who experienced testicular relapse and interrogated their leukemic cells with exome sequencing. The sequencing results and clonality analyses suggest that relapse of patient D483 directly evolved from the leukemic clone at diagnosis which survived chemotherapy. In contrast, relapse leukemia cells (both bone marrow and testis) of patient D727 were likely derived from a common ancestral clone, and testicular relapse likely arose independently from the bone marrow relapsed leukemia. Our findings decipher the mutational spectra and shed light on the clonal evolution of two cases of pediatric ALL with testicular relapse. Presence of CREBBP/NT5C2 mutations suggests that a personalized therapeutic approach should be applied to these two patients.

Managing haematological disorders during pregnancy.

The management of patients with pre-existing haematological diseases during pregnancy can be particularly challenging. The potential maternal and foetal toxicities from treatment regimens including chemotherapy for malignant haematological disorders mean that joint management between obstetricians and haematologists is essential for achieving good outcomes for both mother and baby. Patients with inherited or acquired disorders of haemostasis including platelets (essential thrombocythaemia) and coagulation (antiphospholipid syndrome) resulting in a pro-thrombotic state also require special consideration as pregnancy is generally considered to be a pro-thrombotic condition which could exacerbate the pre-existing disorder. The choice, timing and duration of anticoagulation or anti-platelet therapy require careful coordination during the antenatal, perinatal as well as postnatal periods to ensure that both maternal and foetal risks are taken into consideration. Pregnancy in women with sickle cell disease has long been identified as high risk with medical and pregnancy related risks being more common compared to women without it. A range of foetal risks have also been reported but improvement in outcomes has been seen with better obstetric and haematological care and the emphasis on multidisciplinary teamwork. The meticulous management of iron overload and risks associated with repeated blood transfusions extends into the care of pregnant women with other haemoglobinopathies like thalassemias.