scholarly journals NPM1 MUTATED, BCR-ABL1 POSITIVE MYELOID NEOPLASMS: REVIEW OF LITERATURE

2020 ◽  
Vol 12 (1) ◽  
pp. e2020083
Author(s):  
Gianfranco Catalano ◽  
Pasquale Niscola ◽  
Cristina Banella ◽  
Daniela Diverio ◽  
Malgorzata Monika Trawinska ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Chimeric Protein ◽  
Break Point ◽  
World Health ◽  
Founder Mutations ◽  
Molecular Features ◽  
Hematological Cancers ◽  
Health Organization ◽  
Inhibition Of Differentiation

Break point cluster region - Abelson (BCR-ABL1) chimeric protein and mutated Nucleophosmin (NPM1) are often present in hematological cancers, but they rarely coexist in the same disease. Both anomalies are considered founder mutations causing inhibition of differentiation and apoptosis, but BCR-ABL1 could act as a secondary mutation conferring a proliferative advantage to a pre-neoplastic clone. The 2016 World Health Organization (WHO) classification lists the provisional acute myeloid leukemia (AML) with BCR-ABL1, which must be diagnosed differentially from the rare blast phase (BP) onset of a chronic myeloid leukemia (CML), mainly because of the different therapeutic approach in the use of tyrosine kinase inhibitors (TKI). Here we review all published cases since 1975 and describe a case from our institution in order to discuss the clinical and molecular features of this rare combination, and report the latest acquisition about an occurrence that could pertain either to the rare AML BCR-ABL1 positive or the even rarer CML-BP with mutated NPM1 at onset.

scholarly journals How I treat FLT3-mutated AML

Blood ◽  
2017 ◽  
Vol 129 (5) ◽  
pp. 565-571 ◽  
Author(s):  
Keith W. Pratz ◽  
Mark Levis
Keyword(s):  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
Kinase Inhibitors ◽  
Common Type ◽  
World Health ◽  
Distinct Entity ◽  
Internal Tandem Duplication ◽  
The World ◽  
Health Organization ◽  
Near Future

Abstract FLT3-mutated acute myeloid leukemia (AML), despite not being recognized as a distinct entity in the World Health Organization (WHO) classification system, is readily recognized as a particular challenge by clinical specialists who treat acute leukemia. This is especially true with regards to the patients harboring the most common type of FLT3 mutation, the internal tandem duplication (FLT3-ITD) mutation. Here we present 4 patient cases from our institution and discuss how our management reflects what we have learned about this subtype of the disease. We also reflect on how we anticipate the management might change in the near future, with the emergence of clinically useful tyrosine kinase inhibitors.

scholarly journals A review of current knowledge of myeloproliferative disorders in the horse

2021 ◽  
Vol 63 (1) ◽  
Author(s):  
Katy Satué ◽  
Juan Carlos Gardon ◽  
Ana Muñoz
Keyword(s):  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Current Knowledge ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Disorders ◽  
World Health ◽  
Chronic Granulocytic Leukemia ◽  
Current State ◽  
Multiple Cell ◽  
Health Organization

AbstractMyeloid disorders are conditions being characterized by abnormal proliferation and development of myeloid lineage including granulocytes (neutrophils, eosinophils and basophils), monocytes, erythroids, and megakaryocytes precursor cells. Myeloid leukemia, based on clinical presentation and proliferative rate of neoplastic cells, is divided into acute (AML) and myeloproliferative neoplasms (MPN). The most commonly myeloid leukemia reported in horses are AML-M4 (myelomonocytic) and AML-M5 (monocytic). Isolated cases of AML-M6B (acute erythroid leukemia), and chronic granulocytic leukemia have also been reported. Additionally, bone marrow disorders with dysplastic alterations and ineffective hematopoiesis affecting single or multiple cell lineages or myelodysplastic diseases (MDS), have also been reported in horses. MDSs have increased myeloblasts numbers in blood or bone marrow, although less than 20%, which is the minimum level required for diagnosis of AML. This review performed a detailed description of the current state of knowlegde of the myeloproliferative disorders in horses following the criteria established by the World Health Organization.

scholarly journals Programme for Harmonization to the International Scale in Latin America for BCR-ABL1 quantification in CML patients: findings and recommendations

2020 ◽  
Vol 58 (12) ◽  
pp. 2025-2035
Author(s):  
María Sol Ruiz ◽  
María Belén Sánchez ◽  
Yuly Masiel Vera Contreras ◽  
Evangelina Agrielo ◽  
Marta Alonso ◽  
...  
Keyword(s):  
Latin America ◽  
Myeloid Leukemia ◽  
World Health ◽  
Molecular Response ◽  
Limit Of Quantification ◽  
International Scale ◽  
Deep Molecular Response ◽  
Health Organization ◽  
First Time

AbstractObjectivesThe quantitation of BCR-ABL1 mRNA is mandatory for chronic myeloid leukemia (CML) patients, and RT-qPCR is the most extensively used method in testing laboratories worldwide. Nevertheless, substantial variation in RT-qPCR results makes inter-laboratory comparability hard. To facilitate inter-laboratory comparative assessment, an international scale (IS) for BCR-ABL1 was proposed.MethodsThe laboratory-specific conversion factor (CF) to the IS can be derived from the World Health Organization (WHO) genetic reference panel; however, this material is limited to the manufacturers to produce and calibrate secondary reference reagents. Therefore, we developed secondary reference calibrators, as lyophilized cellular material, aligned to the IS. Our purpose was both to re-evaluate the CF in 18 previously harmonized laboratories and to propagate the IS to new laboratories.ResultsOur field trial including 30 laboratories across Latin America showed that, after correction of raw BCR-ABL1/ABL1 ratios using CF, the relative mean bias was significantly reduced. We also performed a follow-up of participating laboratories by annually revalidating the process; our results support the need for continuous revalidation of CFs. All participating laboratories also received a calibrator to determine the limit of quantification (LOQ); 90% of them could reproducibly detect BCR-ABL1, indicating that these laboratories can report a consistent deep molecular response. In addition, aiming to investigate the variability of BCR-ABL1 measurements across different RNA inputs, we calculated PCR efficiency for each individual assay by using different amounts of RNA.ConclusionsIn conclusion, for the first time in Latin America, we have successfully organized a harmonization platform for BCR-ABL1 measurement that could be of immediate clinical benefit for monitoring the molecular response of patients in low-resource regions.

Lung Tumors With Neuroendocrine Morphology: Essential Radiologic and Pathologic Features

2008 ◽  
Vol 132 (7) ◽  
pp. 1055-1061 ◽  
Author(s):  
Teri J. Franks ◽  
Jeffrey R. Galvin
Keyword(s):  
Neuroendocrine Tumors ◽  
Classification Systems ◽  
World Health ◽  
National Library ◽  
Molecular Features ◽  
Distinct Subset ◽  
Pathologic Features ◽  
The World ◽  
Health Organization

Abstract Context.—Tumors with neuroendocrine morphology are a distinct subset of lung neoplasms sharing characteristic histologic, immunohistochemical, ultrastructural, and molecular features. Objective.—To review the current histologic classification and the diagnostic criteria for the major categories of neuroendocrine tumors of the lung. Data Sources.—Published classification systems from the World Health Organization and pertinent peer-reviewed articles indexed in PubMed (National Library of Medicine) form the basis of this review. Conclusions.—Accurate classification of the neuroendocrine tumors of the lung requires knowledge of specific criteria separating the major categories, which is essential for determining prognosis and treatment.

The Value of CD64 Expression in Distinguishing Acute Myeloid Leukemia With Monocytic Differentiation From Other Subtypes of Acute Myeloid Leukemia: A Flow Cytometric Analysis of 64 Cases

2007 ◽  
Vol 131 (5) ◽  
pp. 748-754
Author(s):  
Cherie H. Dunphy ◽  
Wohzan Tang
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Flow Cytometric Analysis ◽  
World Health ◽  
Monocytic Differentiation ◽  
Flow Cytometric Immunophenotyping ◽  
Cd64 Expression ◽  
Flow Cytometric ◽  
Health Organization ◽  
Acute Myeloid

Abstract Context.—Flow cytometric immunophenotyping is a useful ancillary tool in the diagnosis and subclassification of acute myeloid leukemias (AMLs). A recent study concluded that CD64 is sensitive and specific for distinguishing AMLs with a monocytic component (ie, AML M4 and AML M5) from other AML subtypes. However, in that study, the intensity of CD64 was not well defined and the number of non-M4/non-M5 AMLs was small. Objective.—To evaluate the usefulness of CD64 by flow cytometric immunophenotyping in distinguishing AMLs with monocytic differentiation from other AML subtypes. Design.—Sixty-four AMLs subclassified based on the French-American-British and World Health Organization classifications on pretreatment bone marrows were retrieved from our files (7 M0s, 11 M1s, 17 M2s, 7 M3s, 9 M4s, 7 M5s, 4 M6s, and 2 M7s). A standard panel of markers, including CD2, CD3, CD5, CD7, CD10, CD11b, CD13, CD14, CD15, CD19, CD20, CD33, CD34, CD45, CD56, CD64, CD117, and HLA-DR, were analyzed by flow cytometric immunophenotyping in all AMLs (52 bone marrow samples; 12 peripheral blood samples). Results.—CD64 was expressed in AML subtypes M0 to M5 in varying intensities: heterogeneously expressed in 1 of 7 M0s; dimly expressed in 3 of 11 M1s; dimly and moderately expressed in 6 and 2 of 17 M2s, respectively; dimly and moderately expressed in 5 and 1 of 7 M3s, respectively; dimly expressed in 4 of 9 M4s; and heterogeneously, moderately, and strongly expressed in 1, 3, and 3 of 7 M5s, respectively. Conclusions.—Strong CD64 expression distinguishes AML M5; however, heterogeneous, dim, or moderate expression in itself does not distinguish M0 through M4 subtypes from M5 with dim to moderate CD64 expression. However, any CD64 expression associated with strong CD15 expression distinguishes AML M4 or M5, from other AML subtypes.

Clinico-pathologic characteristics and outcomes of the World Health Organization (WHO) provisional entity de novo acute myeloid leukemia with mutated RUNX1

2020 ◽  
Vol 33 (9) ◽  
pp. 1678-1689
Author(s):  
Andrés E. Quesada ◽  
Guillermo Montalban-Bravo ◽  
Rajyalakshmi Luthra ◽  
Keyur P. Patel ◽  
Koji Sasaki ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
World Health Organization ◽  
Myeloid Leukemia ◽  
De Novo ◽  
World Health ◽  
The World ◽  
Health Organization ◽  
Acute Myeloid

scholarly journals BCR-ABL1–like B-Acute Lymphoblastic Leukemia/Lymphoma: A Comprehensive Review

2019 ◽  
Vol 144 (2) ◽  
pp. 150-155 ◽  
Author(s):  
Sarika Jain ◽  
Anu Abraham
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
World Health Organization ◽  
Kinase Inhibitors ◽  
Lymphoblastic Leukemia ◽  
World Health ◽  
Comprehensive Review ◽  
The World ◽  
Health Organization ◽  
Stimulating Factor

Context.— In the 2016 update of the World Health Organization (WHO) classification of hematopoietic neoplasms, BCR-ABL1–like B-acute lymphoblastic leukemia/lymphoma (B-ALL) is added as a new provisional entity that lacks the BCR-ABL1 translocation but shows a pattern of gene expression very similar to that seen in B-ALL with BCR-ABL1. Objective.— To review the kinase-activating alterations and the diagnostic approach for BCR-ABL1–like B-ALL. Data Sources.— We provide a comprehensive review of BCR-ABL1–like B-ALL based on recent literature and the 2016 update of the World Health Organization classification of hematopoietic neoplasms. Conclusions.— Several types of kinase-activating alterations (fusions or mutations) are identified in BCR-ABL1–like B-ALL. The main categories are alterations in the ABL class family of genes, encompassing ABL1, ABL2, PDGFRB, PDGFRA (rare), and colony-stimulating factor 1 receptor (CSF1R) fusions, or the JAK2 class family of genes, encompassing alterations in JAK2, CRLF2, EPOR, and other genes in this pathway. These alterations determine the sensitivity to tyrosine kinase inhibitors. As a wide variety of genomic alterations are included in this category, the diagnosis of BCR-ABL1–like B-ALL is extremely complex. Stepwise algorithms and comprehensive unbiased testing are the 2 ways to approach the diagnosis of BCR-ABL1–like B-ALL.

Translocation t(11;17) Is Not Always Associated with Acute Myeloid or Acute Promyelocytic Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5044-5044
Author(s):  
Muhamed Baljevic ◽  
Suresh C. Jhanwar ◽  
Todd L. Rosenblat ◽  
Peter G. Maslak ◽  
Dan Douer ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Acute Promyelocytic Leukemia ◽  
Chromosomal Aberration ◽  
Myeloid Leukemia ◽  
Break Point ◽  
Promyelocytic Leukemia ◽  
World Health ◽  
Bone Marrow Morphology ◽  
Acute Myeloid

Abstract Abstract 5044 Translocation t(11;17) is a rare chromosomal aberration that as an isolated entity is not pathognomonic of any hematologic disorder. Within the wide spectrum of chromosomal translocations, it is well recognized, though is uncommon, as a variant of acute promyelocytic leukemia (APL), with specific break-point at the PLZF gene on chromosome 11 forming a fusion gene the PLZF/RAR-α almost invariably resistant to all-trans retinoic acid (ATRA). Abnormal fusion of 11q23 mixed-lineage-leukemia (MLL) gene with the SEPT9 transcript on chromosome 17q25 in an acute monocytic (M5b) variant of acute myeloid leukemia (AML) is another example of an acute leukemia characterized by this chromosomal aberration. Sporadically, it has also been reported as a transient chromosomal break-point (q14;q12) in chronic myeloid leukemia (CML) (Olazábal et al. Cancer Genet Cytogenet. 2008). However, this chromosomal translocation is not well recognized in myelodysplastic syndrome (MDS) though nearly 50% of de novo and 80% of therapy-induced MDS (t-MDS) harbor karyotypic anomalies. In the present study, we report the natural history, clinical characteristics, outcome and the breakpoint regions in 2 patients with MDS and t(11;17) treated at Memorial Sloan-Kettering Cancer Center (MSKCC) between 2000–2011. The first patient is an asymptomatic 28-year-old man presenting with a platelet count of 72,000/μL. The bone marrow morphology was consistent with a MDS, and clonal abnormality with karyotype 46, XY, t(11;17)(p11.2;p13) as a sole abnormality. Molecular analysis was negative for PML/RAR-α RNA transcript. The second patient is a 59-year-old woman who presented with mild fatigue, hemoglobin of 10.6 g/dL, platelet count of 84,000μ/L and was diagnosed with del(5q) MDS. Her bone marrow morphology was consistent with refractory cytopenia with multilineage dysplasia (RCMD) as defined by the World Health Organization (WHO),with an international prognostic scoring system (IPSS) intermediate-1 risk (score of 0.5). Her karyotype showed the translocation t(11;17) as a part of a clonal abnormality with karyotype 46,XX,del(5)(q13q33),t(11;17)(q24;q23). Both patients are being followed without treatment, as the peripheral blood counts are stable. The second patient is being considered for an allogeneic hematopoietic stem cell transplant (HSCT). These 2 patients are examples of non-APL/MLL-AML related translocation t(11;17) with different break-point regions. To our knowledge, there have only been several isolated cases of this translocation in patients with MDS. In this group of reported cases that included 4 women and 2 men (out of which 3 were children), the median age at presentation was 35; 2 cases were primary MDS while other 4 represented either t-MDS, MDS-derived AML, primary acute lymphoblastic leukemia (ALL) or AML. One of the previously reported patients with t(11;17)-related MDS was treated with a single course of decitabine, then subsequently underwent an unrelated-donor HSCT with an assumed favorable long-term outcome (Kreuziger et al. Leuk Res. 2007). Alternatively, the response to treatment in those of AML-M5b subtype and PLZF/RAR-α t(11;17)(q23;q11.12) was very poor (Tetsuya et al. Int J Hematol. 2008; Guidez et al. Leukemia. 1994). Thus, although the course of our 2 MDS patients associated with t(11;17) has been indolent to date, a larger cohort of patients and a longer follow-up is necessary before conclusions regarding prognosis and outcome can be made for this subgroup of patients with MDS. A review of the literature suggests these currently reported patients are the first with these particular break-point variations, and among the first altogether of adults with non-therapy related MDS with translocation t(11;17). Disclosures: No relevant conflicts of interest to declare.

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