Acute myeloid leukemia (AML) is a hematologic malignancy that occurs due to alterations such as genetic mutations, chromosomal translocations, or changes in molecular levels. These alterations can accumulate in stem cells and hematopoietic progenitors, leading to the development of AML, which has a prevalence of 80% of acute leukemias in the adult population. Recurrent cytogenetic abnormalities, in addition to mediating leukemogenesis onset, participate in its evolution and can be used as established diagnostic and prognostic markers. Most of these mutations confer resistance to the traditionally used treatments and, therefore, the aberrant protein products are also considered therapeutic targets. The surface antigens of a cell are characterized through immunophenotyping, which has the ability to identify and differentiate the degrees of maturation and the lineage of the target cell, whether benign or malignant. With this, we seek to establish a relationship according to the molecular aberrations and immunophenotypic alterations that cells with AML present.

Hematopoietic stem cells (HSCs) are known for their ability to proliferate and self-renew, thus being responsible for sustaining the hematopoietic system and residing in the bone marrow (BM). Leukemic stem cells (LSCs) are recognized by their stemness features such as drug resistance, self-renewal, and undifferentiated state. LSCs are also present in BM, being found in only 0.1%, approximately. This makes their identification and even their differentiation difficult since, despite the mutations, they are cells that still have many similarities with HSCs. Although the common characteristics, LSCs are heterogeneous cells and have different phenotypic characteristics, genetic mutations, and metabolic alterations. This whole set of alterations enables the cell to initiate the process of carcinogenesis, in addition to conferring drug resistance and providing relapses. The study of LSCs has been evolving and its application can help patients, where through its count as a biomarker, it can indicate a prognostic factor and reveal treatment results. The selection of a target to LSC therapy is fundamental. Ideally, the target chosen should be highly expressed by LSCs, highly selective, absence of expression on other cells, in particular HSC, and preferentially expressed by high numbers of patients. In view of the large number of similarities between LSCs and HSCs, it is not surprising that current treatment approaches are limited. In this mini review we seek to describe the immunophenotypic characteristics and mechanisms of resistance presented by LSCs, also approaching possible alternatives for the treatment of patients.

The WD repeat containing antisense to TP53 (WRAP53) gene codifies an antisense transcript for tumor protein p53 (TP53), stabilization (WRAP53α), and a functional protein (WRAP53β, WDR79, or TCAB1). The WRAP53β protein functions as a scaffolding protein that is important for telomerase localization, telomere assembly, Cajal body integrity, and DNA double-strand break repair. WRAP53β is one of many proteins known for containing WD40 domains, which are responsible for mediating a variety of cell interactions. Currently, WRAP53 overexpression is considered a biomarker for a diverse subset of cancer types, and in this study, we describe what is known about WRAP53β’s multiple interactions in cell protein trafficking, Cajal body formation, and DNA double-strand break repair and its current perspectives as a biomarker for cancer.

Multiple myeloma (MM) is a blood cell neoplasm characterized by excessive production of malignant monoclonal plasma cells (activated B lymphocytes) by the bone marrow, which end up synthesizing antibodies or antibody fragments, called M proteins, in excess. The accumulation of this production, both cells themselves and of the immunoglobulins, causes a series of problems for the patient, of a systemic and local nature, such as blood hyperviscosity, renal failure, anemia, bone lesions, and infections due to compromised immunity. MM is the third most common hematological neoplasm, constituting 1% of all cancer cases, and is a disease that is difficult to treat, still being considered an incurable disease. The treatments currently available cannot cure the patient, but only extend their lifespan, and the main and most effective alternative is autologous hematopoietic stem cell transplantation, but not every patient is eligible, often due to age and pre-existing comorbidities. In this context, the search for new therapies that can bring better results to patients is of utmost importance. Protein tyrosine kinases (PTKs) are involved in several biological processes, such as cell growth regulation and proliferation, thus, mutations that affect their functionality can have a great impact on crucial molecular pathways in the cells, leading to tumorigenesis. In the past couple of decades, the use of small-molecule inhibitors, which include tyrosine kinase inhibitors (TKIs), has been a hallmark in the treatment of hematological malignancies, and MM patients may also benefit from TKI-based treatment strategies. In this review, we seek to understand the applicability of TKIs used in MM clinical trials in the last 10 years.

The detection of genetic alterations in patients with acute leukemias is essential for the targeting of more specific and effective therapies. Therefore, the aim of this study was to compare the sensitivity of Nested-PCR and RT-qPCR techniques in the detection of genetic alterations in patients with acute leukemias. This study included samples from 117 patients treated at the Fortaleza General Hospital. All samples were submitted to analysis using the Nested-PCR and the RT-qPCR techniques. Acute Myeloid Leukemia (AML) patients’ samples were submitted to the analysis of the following alterations: FLT3-ITD, RUNX1::RUNX1T1, CBFB::MYH11 and PML::RARA; meanwhile, BCR::ABL1, TCF3::PBX1, KMT2A::AFF1, ETV6::RUNX1, and STIL::TAL1 fusions were investigated in the Acute Lymphoblastic Leukemia (ALL) patients’ samples. Throughout the study, 77 patients were diagnosed with AML and 40 with ALL. Among the 77 AML patients, FLT3-ITD, RUNX1::RUNX1T1, PML::RARA, and CBFB::MYH11 were detected in 4, 7, 10 and 8 patients, respectively. Among the 40 ALL patients, the presence of 23 patients with BCR::ABL1 translocation and 9 patients with TCF3::PBX1 translocation was observed through the RT-qPCR methodology. Overall, the present study demonstrated that the RT-qPCR technique presented a higher sensitivity when compared to the Nested-PCR technique at the time of diagnosis of the acute leukemia samples studied.

Acute leukemias are highly aggressive hematologic malignancies that demand intensive chemotherapy regimens. However, drug toxicity remains a major barrier to treatment success and patient survival. In this context, pharmacogenomics offers a promising strategy by identifying single-nucleotide variants (SNVs) that influence drug metabolism, efficacy, and toxicity, ultimately impacting treatment outcomes. This study analyzed data from the ClinPGx/PharmGKB database to identify clinically annotated variants related to chemotherapy response in Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL). A total of 24 variants were curated for AML and 57 for ALL. Among these, nonsynonymous variants were most frequent in ALL (31.6%), while synonymous variants predominated in AML (33.3%). Although traditionally considered neutral, synonymous and intronic variants may influence gene expression through regulatory or splicing mechanisms. The analysis revealed clinically significant variants associated with chemotherapy response, particularly in the ABCB1 gene, observed in 12.5% of AML and 10.5% of ALL cases. Several variants, particularly TPMT, NUDT15, ABCC1, SLC28A3, and RARG, were associated with severe adverse effects such as myelotoxicity, mucositis, cardiotoxicity, and hepatotoxicity. This study reinforces the importance of genetic variants in modulating the therapeutic response and toxicity to chemotherapy drugs in acute leukemias. Analysis of ClinPGx/PharmGKB data emphasizes ABCB1 as a potential resistance marker and supports pre-treatment genotyping of genes like TPMT and NUDT15 to prevent severe toxicities. Future advances should include the expansion of pharmacogenetic studies in underrepresented populations and the clinical validation of new markers in prospective trials, aiming to consolidate precision medicine as a routine part of the therapeutic management of acute leukemias.