Issue Archive

CRLF2-rearranged acute lymphoblastic leukemia (ALL) is the largest subset of Philadelphhia chromosome–like ALL and is associated with poor outcomes. CRLF2-rearranged ALL is associated with activation of Janus kinase (JAK)–STAT pathways, but JAK inhibitors are of limited treatment efficacy. In a Plenary Paper, Chang et al demonstrate that targeting Janus kinases for degradation is effective against cell lines and xenograft models of JAK-STAT-driven ALL resistant to JAK inhibitors.

Long noncoding RNAs (lncRNAs) are increasingly recognized as regulators of genome structure and transcriptional activity. Furthermore, many lncRNAs are aberrantly expressed in cancer and may contribute to malignant transformation. Qiu et al review the current understanding of lncRNAs, their role in gene regulation, and the consequent insights into the pathophysiology of hematologic malignancy.

GATA1-mutant myeloid leukemia in Down syndrome (ML-DS) has high rates of event-free survival (EFS) with chemotherapy. Attempts to reduce treatment intensity to limit infectious morbidity have been made. Hitzler and colleagues report results of a trial in which patients with negative measurable residual disease by flow cytometry after first induction did not receive high dose AraC (HD-AraC). Unfortunately, while survival was still excellent, patients who did not receive HD-AraC had significantly poorer EFS and poor survival after relapse.

STAT5A and STAT5B are transcription factors important in both normal hematopoiesis and leukemia. They are 95% homologous and assumed to have overlapping function. Kollmann et al report a unique role for STAT5B in the self-renewal of both hematopoietic and leukemic stem cells by induction of genes associated with quiescence and renewal, including CD9. CD9 is a poor prognostic marker in STAT5-driven leukemia and may be a useful therapeutic target.

Complex karyotype predicts impaired survival after ibrutinib or venetoclax in relapsed/refractory (RR) chronic lymphocytic leukemia (CLL). Kittai et al assessed the prognostic impact of increasing karyotypic complexity and clonal evolution in both treatment-naïve and RR patients. They confirm the importance of karyotype pretherapy and the further impact of clonal evolution in the subsequent risk of progression and death.

Lee-Sundlov and colleagues elucidate a role for sialic acid changes in regulating platelet number in thrombocytopenic states such as immune thrombocytopenia (ITP). They demonstrate antibody against Thomsen-Friedenreich (TF) antigen in plasma from pediatric patients with ITP and delineate a role for immune cells in recognizing altered sialylation of aberrant exposed TF antigen in regulating thrombopoiesis through interferon release.

Primary cytotoxic T cell lymphomas (CTCLs) are a rare subset of aggressive, poor-prognosis T-cell lymphomas targeting the skin; they include primary cutaneous γδT-cell lymphoma, primary cutaneous VD8⁺ aggressive epidermotropic T cell lymphoma (PCAETCL), and cytotoxic CTCL not otherwise specified. Lee et al report that all 3 subsets have JAK-STAT activation, but PCAETCL uniquely carries JAK2 gene fusions that may render them especially susceptible to JAK inhibitors.