Anti-CD7 monoclonal antibody, clone 477DU39.3.4

Primary immunodeficiency diseases comprise a group of heterogeneous genetic defects that affect immune system development and/or function. Here we use in vitro differentiation of human induced pluripotent stem cells (iPSCs) generated from patients with different recombination-activating gene 1 (RAG1) mutations to assess T-cell development and T-cell receptor (TCR) V(D)J recombination. RAG1-mutants from severe combined immunodeficient (SCID) patient cells showed a failure to sustain progression beyond the CD3(--)CD4(-)CD8(-)CD7(+)CD5(+)CD38(-)CD31(-/lo)CD45RA(+) stage of T-cell development to reach the CD3(-/+)CD4(+)CD8(+)CD7(+)CD5(+)CD38(+)CD31(+)CD45RA(-) stage. Despite residual mutant RAG1 recombination activity from an Omenn syndrome (OS) patient, similar impaired T-cell differentiation was observed, due to increased single-strand DNA breaks that likely occur due to heterodimers consisting of both an N-terminal truncated and a catalytically dead RAG1. Furthermore, deep-sequencing analysis of TCR-beta (TRB) and TCR-alpha (TRA) rearrangements of CD3(-)CD4(+)CD8(-) immature single-positive and CD3(+)CD4(+)CD8(+) double-positive cells showed severe restriction of repertoire diversity with preferential usage of few Variable, Diversity, and Joining genes, and skewed length distribution of the TRB and TRA complementary determining region 3 sequences from SCID and OS iPSC-derived cells, whereas control iPSCs yielded T-cell progenitors with a broadly diversified repertoire. Finally, no TRA/delta excision circles (TRECs), a marker of TRA/delta locus rearrangements, were detected in SCID and OS-derived T-lineage cells, consistent with a pre-TCR block in T-cell development. This study compares human T-cell development of SCID vs OS patients, and elucidates important differences that help to explain the wide range of immunologic phenotypes that result from different mutations within the same gene of various patients. (Blood. 2016;128(6):783-793)

OBJECTIVE: Several factors are known to affect prognosis of acute leukemia such as age, high leukocyte count, cytogenetic abnormality, performance status and recurrent leukemia. We aimed to investigate the association between cell surface markers and prognostic determinants such as recurrence at 6 and 12 months and survival at 6, 12 and 18 months in acute leukemia patients. PATIENTS AND METHODS: A total of 142 patients, 101 with acute myeloid leukemia (AML) and 41 with B-cell acute lymphoblastic leukemia (B-ALL) were included. The effects of surface markers on survival and recurrence rates were evaluated retrospectively. RESULTS: In AML patients, CD5+ and CD34+ immunophenotypes and in ALL patients cCD22+, CD34+ and CD49f + CD19+ immunophenotypes were positive prognostic indicators. In AML patients CD7 expression, and in ALL patients CD5+, CD7+ and CD117+ immunophenotypes and >90% CD45 expression were negative prognostic indicators. CONCLUSIONS: This study demonstrates that flow cytometry, a common diagnostic tool in acute leukemia, may also have prognostic value in acute leukemia in the future.