Mutation of the tumor suppressor gene, TP53, is associated with abysmal survival outcomes in acute myeloid leukemia (AML). Although it is the most commonly mutated gene in cancer, its occurrence is observed in only 5–10% of de novo AML, and in 30% of therapy related AML (t-AML). TP53 mutation serves as a prognostic marker of poor response to standard-of-care chemotherapy, particularly in t-AML and AML with complex cytogenetics. In light of a poor response to traditional chemotherapy and only a modest improvement in outcome with hypomethylation-based interventions, allogenic stem cell transplant is routinely recommended in these cases, albeit with a response that is often short lived. Despite being frequently mutated across the cancer spectrum, progress and enthusiasm for the development of p53 targeted therapeutic interventions is lacking and to date there is no approved drug that mitigates the effects of TP53 mutation. There is a mounting body of evidence indicating that p53 mutants differ in functionality and form from typical AML cases and subsequently display inconsistent responses to therapy at the cellular level. Understanding this pathobiological activity is imperative to the development of effective therapeutic strategies. This review aims to provide a comprehensive understanding of the effects of TP53 on the hematopoietic system, to describe its varying degree of functionality in tumor suppression, and to illustrate the need for the adoption of personalized therapeutic strategies to target distinct classes of the p53 mutation in AML management.

Mixed-phenotype acute leukemia (MPAL) comprises a heterogenous group of leukemias that are genetically, immunophenotypically, and clinically, diverse. Given the rarity of the disease, the diagnosis and treatment of MPAL is extremely challenging. Recent collaborative efforts have made significant progress in understanding the complex genomic landscape of MPAL. Some retrospective studies support starting ALL-type induction followed by an allogeneic stem cell transplant(allo-sct) in the first complete remission; however, due to the inherent bias of retrospective data and small case series, a prospective validation of AML- and ALL-based regimen, and the incorporation of targeted therapies based on genetics and immunophenotype are warranted. The prognosis of adults and children with MPAL varies; this justifies modulating the intensity of therapy, including the use of allo-sct as a consolidation strategy.

Blast crisis (BC) is one of the most dreaded complications of chronic myeloid leukemia (CML). Fortunately, the incidence of BC has diminished markedly in the BCR-ABL tyrosine kinase inhibitor (TKI) era. The primary objective of initial treatment in BC is to achieve a second chronic phase (CP) and to proceed to an allogeneic stem cell transplantation (SCT) in eligible patients. The clinical outcome of patients with CML BC remains unsatisfactory, even with highly potent TKIs, as remissions are short lived and there is an unmet need for novel therapies. We provide a comprehensive summary reviewing the current management of Lymphoid BC.

Despite the major advancements in the management of chronic phase (CP) chronic myeloid leukemia (CML), blast crisis (BC) remains a major therapeutic challenge. BC can be myeloid, lymphoid, or mixed lineage with myeloid BC being the most common type. BC in CML is mediated by aberrant tyrosine kinase activity of the BCR::ABL fusion protein. The introduction of BCR::ABL tyrosine kinase inhibitor (TKI) has been a gamechanger in the treatment of CML and there has been a significant reduction in the incidence of BC. The main treatment goal in BC is to achieve a second CP and consolidate that with an allogeneic stem cell transplantation (SCT) in eligible patients. The outcomes in BC remain dismal even in the current era. In this review, we provide an overview of the biology and current therapeutic approach in myeloid BC.

The established protocol for the management of acute myeloid leukemia (AML) has traditionally involved the administration of induction chemotherapy, followed by consolidation chemotherapy, and subsequent allogeneic stem cell transplantation for eligible patients. However, the prognosis for individuals with relapsed and refractory AML remains unfavorable. In response to the necessity for more efficacious therapeutic modalities, targeted immunotherapy has emerged as a promising advancement in AML treatment. This comprehensive review article specifically examines classical unconjugated and toxin-conjugated monoclonal antibodies, which are currently in the preclinical phase or undergoing evaluation in clinical trials. The review delves into the proposed mechanisms through which these monoclonal antibodies elicit anti-tumor activity and identifies the challenges associated with designing targeted immunotherapy. The review focuses on targeting specific antigens in AML, including FLT3/CD125, CLL-1, CD33, CD38, CD47, CD70, and CD123.

Therapy-related acute myeloid leukemia (t-AML) usually stems from exposure of the bone marrow to cytotoxic chemotherapy and/or radiation therapy. t-AML is usually associated with poor overall survi... Plan language summary Acute myeloid leukemia (AML) is a type of cancer of the white blood cells. AML can rarely arise from prior treatment with radiation and/or chemotherapy and are referred to as ...