Adult acute megakaryoblastic leukemia: rare association with cytopenias of undetermined significance and p210 and p190&lt;em&gt; BCR&amp;ndash;ABL&lt;/em&gt; transcripts

Dima, Delia; Oprita, Liana; Rosu, Ana-Maria; Selicean, Cristina; Moisoiu, Vlad; Frinc, Ioana; Zdrenghea, Dumitru; Tomuleasa, Ciprian

doi:10.2147/ott.s146973

Cited by 11 publications

(14 citation statements)

References 18 publications

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“…Therapy for acute leukemias, both myeloid and lymphoblastic, has become increasingly effective in the past decade (1)(2)(3)(4)(5)(6)(7). This is explained by the increasing efforts of personalizing chemotherapy treatment and supportive care that continuously adapts to initial diagnostic and progression of the disease, and which has resulted in better quality of life and higher overall survival (OS) rate in leukemic patients (8)(9)(10)(11).…”

Section: Background On the Central Nervous Systems (Cns) Involvement In Acute Leukemiasmentioning

confidence: 99%

A narrative review of central nervous system involvement in acute leukemias

Deak¹,

Gorcea-Andronic²,

Sas³

et al. 2021

Ann Transl Med

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Acute leukemias (both myeloid and lymphoblastic) are a group of diseases for which each year more successful therapies are implemented. However, in a subset of cases the overall survival (OS) is still exceptionally low due to the infiltration of leukemic cells in the central nervous system (CNS) and the subsequent formation of brain tumors. The CNS involvement is more common in acute lymphocytic leukemia (ALL), than in adult acute myeloid leukemia (AML), although the rates for the second case might be underestimated. The main reasons for CNS invasion are related to the expression of specific adhesion molecules (VLA-4, ICAM-1, VCAM, L-selectin, PECAM-1, CD18, LFA-1, CD58, CD44, CXCL12) by a subpopulation of leukemic cells, called "sticky cells" which have the ability to interact and adhere to endothelial cells. Moreover, the microenvironment becomes hypoxic and together with secretion of VEGF-A by ALL or AML cells the permeability of vasculature in the bone marrow increases, coupled with the disruption of blood brain barrier. There is a single subpopulation of leukemia cells, called leukemia stem cells (LSCs) that is able to resist in the new microenvironment due to its high adaptability. The LCSs enter into the arachnoid, migrate, and intensively proliferate in cerebrospinal fluid (CSF) and consequently infiltrate perivascular spaces and brain parenchyma. Moreover, the CNS is an immune privileged site that also protects leukemic cells from chemotherapy. CD56/NCAM is the most important surface molecule often overexpressed by leukemic stem cells that offers them the ability to infiltrate in the CNS. Although

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Section: Background On the Central Nervous Systems (Cns) Involvement In Acute Leukemiasmentioning

confidence: 99%

A narrative review of central nervous system involvement in acute leukemias

Deak¹,

Gorcea-Andronic²,

Sas³

et al. 2021

Ann Transl Med

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“…The type of malignant cell is defined according to the lineage, whether it is myeloid, lymphoid or mixed. Acute leukemias also occur when a hematopoietic stem cell acquires a sequence of mutations that confer an advantage of clonal proliferation (43, 48–52). The incidence of AML increases with age and represents 80% of adult leukemia (53) and 15–20% of childhood acute leukemiac (54).…”

Section: Cytogenetics In the Clinic For Myeloid Malignanciesmentioning

confidence: 99%

Long Non-coding RNAs in Myeloid Malignancies

et al. 2019

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Acute myeloid leukemia (AML) represents 80% of adult leukemias and 15–20% of childhood leukemias. AML are characterized by the presence of 20% blasts or more in the bone marrow, or defining cytogenetic abnormalities. Laboratory diagnoses of myelodysplastic syndromes (MDS) depend on morphological changes based on dysplasia in peripheral blood and bone marrow, including peripheral blood smears, bone marrow aspirate smears, and bone marrow biopsies. As leukemic cells are not functional, the patient develops anemia, neutropenia, and thrombocytopenia, leading to fatigue, recurrent infections, and hemorrhage. The genetic background and associated mutations in AML blasts determine the clinical course of the disease. Over the last decade, non-coding RNAs transcripts that do not codify for proteins but play a role in regulation of functions have been shown to have multiple applications in the diagnosis, prognosis and therapeutic approach of various types of cancers, including myeloid malignancies. After a comprehensive review of current literature, we found reports of multiple long non-coding RNAs (lncRNAs) that can differentiate between AML types and how their exogenous modulation can dramatically change the behavior of AML cells. These lncRNAs include: H19, LINC00877, RP11-84C10, CRINDE, RP11848P1.3, ZNF667-AS1, AC111000.4-202, SFMBT2, LINC02082-201, MEG3, AC009495.2, PVT1, HOTTIP, SNHG5, and CCAT1. In addition, by performing an analysis on available AML data in The Cancer Genome Atlas (TCGA), we found 10 lncRNAs with significantly differential expression between patients in favorable, intermediate/normal, or poor cytogenetic risk categories. These are: DANCR, PRDM16-DT, SNHG6, OIP5-AS1, SNHG16, JPX, FTX, KCNQ1OT1, TP73-AS1, and GAS5. The identification of a molecular signature based on lncRNAs has the potential for have deep clinical significance, as it could potentially help better define the evolution from low-grade MDS to high-grade MDS to AML, changing the course of therapy. This would allow clinicians to provide a more personalized, patient-tailored therapeutic approach, moving from transfusion-based therapy, as is the case for low-grade MDS, to the introduction of azacytidine-based chemotherapy or allogeneic stem cell transplantation, which is the current treatment for high-grade MDS.

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“…An important role in homogenizing and standardizing the flow-cytometry-based detection of MRD in acute leukemia was proposed by the European BIOMED-1 Concerted Action, which defined protocols for identifying normal subsets of B, T, and myeloid cells in bone marrow, the starting point for subsequent studies of the aberrant immunophenotypes involved in ALL. These efforts provided an excellent basis for standardized flow cytometric MRD studies in multicenter international treatment protocols for precursor-B-cell ALL and T-cell ALL patients, first by defining a normal pattern, and second, by establishing pathology-based patterns and optimal reagent combinations [137,138,139,140,141,142,143,144,145,146,147,148,149,150,151,152,153,154].…”

Section: Measurable Residual Diseasementioning

confidence: 99%

Approach to the Adult Acute Lymphoblastic Leukemia Patient

Sas

Moisoiu

Teodorescu

et al. 2019

JCM

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During recent decades, understanding of the molecular mechanisms of acute lymphoblastic leukemia (ALL) has improved considerably, resulting in better risk stratification of patients and increased survival rates. Age, white blood cell count (WBC), and specific genetic abnormalities are the most important factors that define risk groups for ALL. State-of-the-art diagnosis of ALL requires cytological and cytogenetical analyses, as well as flow cytometry and high-throughput sequencing assays. An important aspect in the diagnostic characterization of patients with ALL is the identification of the Philadelphia (Ph) chromosome, which warrants the addition of tyrosine kinase inhibitors (TKI) to the chemotherapy backbone. Data that support the benefit of hematopoietic stem cell transplantation (HSCT) in high risk patient subsets or in late relapse patients are still questioned and have yet to be determined conclusive. This article presents the newly published data in ALL workup and treatment, putting it into perspective for the attending physician in hematology and oncology.

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Adult acute megakaryoblastic leukemia: rare association with cytopenias of undetermined significance and p210 and p190<em> BCR–ABL</em> transcripts

Cited by 11 publications

References 18 publications

A narrative review of central nervous system involvement in acute leukemias

A narrative review of central nervous system involvement in acute leukemias

Long Non-coding RNAs in Myeloid Malignancies

Approach to the Adult Acute Lymphoblastic Leukemia Patient

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