scholarly journals How I diagnose and treat NPM1-mutated AML

Blood ◽  
2020 ◽  
Author(s):  
Brunangelo Falini ◽  
Lorenzo Brunetti ◽  
Maria Paola Martelli
Keyword(s):  
Myeloid Leukemia ◽  
Residual Disease ◽  
World Health ◽  
Gene Encoding ◽  
Multifunctional Protein ◽  
Myeloid Neoplasms ◽  
Mutational Status ◽  
Therapeutic Decisions ◽  
Health Organization

Mutations of the nucleophosmin (NPM1) gene, encoding for a nucleolar multifunctional protein, occur in about one-third of adult acute myeloid leukemia (AML). NPM1-mutated AML exhibits unique molecular, pathological and clinical features, that led to its recognition as distinct entity in the 2017 World Health Organization (WHO) classification of myeloid neoplasms. Although WHO criteria for the diagnosis of NPM1-mutated AML are well established, its distinction from other AML entities may be sometimes difficult. Moreover, the percentage of blasts required to diagnose NPM1-mutated AML remains controversial. According to the European LeukemiaNet (ELN), determining the mutational status of NPM1 (together with FLT3) is mandatory for accurate relapse risk assessment. NPM1 mutations are ideal targets for measurable residual disease (MRD) monitoring since they are AML-specific, frequent, very stable at relapse and do not drive clonal hematopoiesis of undetermined significance. MRD monitoring by quantitative PCR of NPM1 mutant transcripts, possibly combined with the ELN genetic-based risk stratification, can guide therapeutic decisions at post-remission stage. Furthermore, immunohistochemistry can be very useful in selected situations, such as diagnosis of NPM1-mutated myeloid sarcoma. Herein, we present four illustrative cases of NPM1-mutated AML, with the aim to address important issues on the biology, diagnosis and therapy of this common form of leukemia.

scholarly journals Diagnostic and therapeutic pitfalls in NPM1-mutated AML: notes from the field

Leukemia ◽  
2021 ◽  
Author(s):  
Brunangelo Falini ◽  
Sofia Sciabolacci ◽  
Lorenza Falini ◽  
Lorenzo Brunetti ◽  
Maria Paola Martelli
Keyword(s):  
Residual Disease ◽  
World Health ◽  
Controversial Issues ◽  
Distinct Entity ◽  
Therapeutic Decisions ◽  
Risk Stratification Model ◽  
Genetic Abnormalities ◽  
Health Organization ◽  
Chronic Myelomonocytic Leukaemia

AbstractMutations of Nucleophosmin (NPM1) are the most common genetic abnormalities in adult acute myeloid leukaemia (AML), accounting for about 30% of cases. NPM1-mutated AML has been recognized as distinct entity in the 2017 World Health Organization (WHO) classification of lympho-haematopoietic neoplasms. WHO criteria allow recognition of this leukaemia entity and its distinction from AML with myelodysplasia-related changes, AML with BCR-ABL1 rearrangement and AML with RUNX1 mutations. Nevertheless, controversial issues include the percentage of blasts required for the diagnosis of NPM1-mutated AML and whether cases of NPM1-mutated myelodysplasia and chronic myelomonocytic leukaemia do exist. Evaluation of NPM1 and FLT3 status represents a major pillar of the European LeukemiaNet (ELN) genetic-based risk stratification model. Moreover, NPM1 mutations are particularly suitable for assessing measurable residual disease (MRD) since they are frequent, stable at relapse and do not drive clonal haematopoiesis. Ideally, combining monitoring of MRD with the ELN prognostication model can help to guide therapeutic decisions. Here, we provide examples of instructive cases of NPM1-mutated AML, in order to provide criteria for the appropriate diagnosis and therapy of this frequent leukaemia entity.

scholarly journals Myeloid Neoplasm With Germline Predisposition: A 2016 Update for Pathologists

2018 ◽  
Vol 143 (1) ◽  
pp. 13-22 ◽  
Author(s):  
Juehua Gao ◽  
Shunyou Gong ◽  
Yi-Hua Chen
Keyword(s):  
Myeloid Leukemia ◽  
Short Review ◽  
World Health ◽  
World Health Organization Classification ◽  
Myeloid Neoplasm ◽  
Myeloid Neoplasms ◽  
Unique Approach ◽  
Health Organization

Context.— Myeloid neoplasms with familial occurrence have been rarely reported in the past. With the advance of molecular technology and better understanding of the molecular pathogenesis of myeloid neoplasms, investigating the genetic causes of familial acute myeloid leukemia or myelodysplastic syndrome has become feasible in the clinical setting. Recent studies have identified a rapidly expanding list of germline mutations associated with increased risks of developing myeloid neoplasm in the affected families. It is important to recognize these entities, as such a diagnosis may dictate a unique approach in clinical management and surveillance for the patients and carriers. Objective.— To raise the awareness of myeloid neoplasms arising in the setting of familial inheritance among practicing pathologists. Data Sources.— Based on recent literature and the 2016 revision of the World Health Organization classification of hematopoietic neoplasms, we provide an up-to-date review of myeloid neoplasm with germline predisposition. Conclusions.— This short review focuses on the clinical, pathologic, and molecular characterization of myeloid neoplasm with germline predisposition. We emphasize the important features that will help practicing pathologists to recognize these newly described entities.

Practical Implications of the 2016 Revision of the World Health Organization Classification of Lymphoid and Myeloid Neoplasms and Acute Leukemia

2017 ◽  
Vol 35 (23) ◽  
pp. 2708-2715 ◽  
Author(s):  
John P. Leonard ◽  
Peter Martin ◽  
Gail J. Roboz
Keyword(s):  
Acute Leukemia ◽  
Clinical Trial Design ◽  
Daily Practice ◽  
World Health ◽  
Myeloid Neoplasms ◽  
New Information ◽  
Health Organization ◽  
Key Aspects ◽  
Practical Implications

A major revision of the WHO classification of lymphoid and myeloid neoplasms and acute leukemia was released in 2016. A key motivation for this update was to include new information available since the 2008 version with clinical relevance for the diagnosis, prognosis, and therapy of patients. With > 100 entities described, it is important for the clinician to understand features that may be important in daily practice, whereas researchers need to incorporate the new classification scheme into study development and analysis. In this review, we highlight the key aspects of the 2016 update with particular importance to routine patient care and clinical trial design.

scholarly journals Flow cytometry in the diagnosis of plasma cell tumors and assessment of minimal residual disease

2021 ◽  
Vol 16 (3) ◽  
pp. 16-25
Author(s):  
L. Yu. Grivtsova ◽  
T. Yu. Mushkarina ◽  
V. V. Lunin ◽  
P. A. Zeynalova
Keyword(s):  
Minimal Residual Disease ◽  
Plasma Cell ◽  
Residual Disease ◽  
World Health ◽  
Hematopoietic Tissue ◽  
Flow Cytometric ◽  
Plasma Cell Neoplasms ◽  
Health Organization ◽  
Minimal Residual

The article considers the features and possibilities of flow cytometric diagnostics of plasma cell neoplasms, taking into account the classification of lymphoid and hematopoietic tissue tumors of the World Health Organization, revision of 2017 and the NCCN clinical recommendations, 2021. Standardized flow cytometric protocols (the Euro-Flow conception) and algorithms for both the diagnosis of plasma cell tumors and the detection of minimal residual disease in plasma cell myeloma are described.

scholarly journals Molecular Pathogenesis in Myeloid Neoplasms with Germline Predisposition

Life ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 46
Author(s):  
Juehua Gao ◽  
Yihua Chen ◽  
Madina Sukhanova
Keyword(s):  
Myeloid Leukemia ◽  
Molecular Mechanisms ◽  
Clinical Presentation ◽  
World Health ◽  
Myeloid Neoplasms ◽  
Increased Risk ◽  
Germline Genes ◽  
Classification Of Tumors ◽  
Inherited Mutations

Myeloid neoplasms with germline predisposition have recently been added as distinct provisional entities in the 2017 revision of the World Health Organization’s classification of tumors of hematopoietic and lymphatic tissue. Individuals with germline predisposition have increased risk of developing myeloid neoplasms—mainly acute myeloid leukemia and myelodysplastic syndrome. Although the incidence of myeloid neoplasms with germline predisposition remains poorly defined, these cases provide unique and important insights into the biology and molecular mechanisms of myeloid neoplasms. Knowledge of the regulation of the germline genes and their interactions with other genes, proteins, and the environment, the penetrance and clinical presentation of inherited mutations, and the longitudinal dynamics during the process of disease progression offer models and tools that can further our understanding of myeloid neoplasms. This knowledge will eventually translate to improved disease sub-classification, risk assessment, and development of more effective therapy. In this review, we will use examples of these disorders to illustrate the key molecular pathways of myeloid neoplasms.

The World Health Organization (WHO) classification of the myeloid neoplasms

Blood ◽  
2002 ◽  
Vol 100 (7) ◽  
pp. 2292-2302 ◽  
Author(s):  
James W. Vardiman ◽  
Nancy Lee Harris ◽  
Richard D. Brunning
Keyword(s):  
World Health Organization ◽  
Who Classification ◽  
World Health ◽  
Classification Schemes ◽  
Myeloid Neoplasms ◽  
Lymphoid Neoplasms ◽  
The World ◽  
Health Organization ◽  
Collaborative Efforts

A World Health Organization (WHO) classification of hematopoietic and lymphoid neoplasms has recently been published. This classification was developed through the collaborative efforts of the Society for Hematopathology, the European Association of Hematopathologists, and more than 100 clinical hematologists and scientists who are internationally recognized for their expertise in hematopoietic neoplasms. For the lymphoid neoplasms, this classification provides a refinement of the entities described in the Revised European-American Lymphoma (REAL) Classification—a system that is now used worldwide. To date, however, there has been no published explanation or rationale given for the WHO classification of the myeloid neoplasms. The purpose of this communication is to outline briefly the WHO classification of malignant myeloid diseases, to draw attention to major differences between it and antecedent classification schemes, and to provide the rationale for those differences.

Sign in / Sign up

Export Citation Format

Share Document