Chronic neutrophilic leukemia: 2020 update on diagnosis, molecular genetics, prognosis, and management

Abstract

Disease overview: Chronic neutrophilic leukemia (CNL) is a rare, often aggressive myeloproliferative neoplasm (MPN) defined by persistent mature neutrophilic leukocytosis, bone marrow granulocyte hyperplasia, and frequent hepatosplenomegaly. The seminal discovery of oncogenic driver mutations in colony-stimulating factor 3 receptor (CSF3R) in the majority of patients with CNL in 2013 anchored a new scientific framework, deepening our understanding of its molecular pathogenesis, providing a diagnostic biomarker, and rationalizing the use of pharmacological targeting. Diagnostic criteria: In 2016, the World Health Organization (WHO) included the presence of activating CSF3R mutations as a central diagnostic feature of CNL. Other criteria include leukocytosis of ≥25 × 10 9 /L comprising >80% neutrophils with <10% circulating precursors and rare blasts, and absence of dysplasia or monocytosis, while not fulfilling criteria for other MPN.Disease updates: Increasingly comprehensive genetic profiling of CNL has disclosed a complex genomic landscape and additional prognostically relevant mutational combinations. Though prognostic determination and therapeutic decision-making remain challenging, emerging data on prognostic markers and the use of newer therapeutic agents, such as JAK inhibitors, are helping to define state-of-the-art management in CNL.

Manifestações orais nas doenças mieloproliferativas: Uma revisão de literatura

“…Seu diagnóstico é difícil de distinguir entre a relação entre a LMC, onde um estudo citogenético é de crucial importância para a diferenciação entre LNC e LMC (Szuber et al, 2020).…”

“…Onde normalmente afeta pacientes de ambos os sexos, alterando assim os níveis de fosfatase alcalina e vitamina B12. Da mesma forma, pode ocorrer transformação para outras síndromes mieloproliferativas (Szuber et al, 2020;Szuber & Tefferi, 2018).…”

“…Quando falamos de sintomas, são bem semelhantes a LMC incluindo fadiga, perda de peso, mal-estar, fácil saciedade e dor do quadrante superior esquerdo (Melo & Gonçalves, 2016;Szuber et al, 2020).…”

Chronic Neutrophilic Leukemia: A Literature Review of the Rare Myeloproliferative Pathology

“…The WHO diagnostic criteria of 2016 for CNL was formulated to rule out the likelihood of secondary or clonal neutrophilia, which may be seen in myeloid malignancies apart from CNL [8]. The management of CNL presently does not have an established standard of care [9]. Drugs such as hydroxyurea are used as first-line chemotherapy but have not always provided a stable response [10].…”

CSF3R T618I mutant chronic myelomonocytic leukemia (CMML) defines a proliferative CMML subtype enriched in ASXL1 mutations with adverse outcomes

“…CSF3R T618I mutant chronic myelomonocytic leukemia (CMML) defines a proliferative CMML subtype enriched in ASXL1 mutations with adverse outcomes Evandro D. Bezerra 1 , Terra L. Lasho 1 , Christy M. Finke 1 , Antoine N. Saliba 1 , Michelle A. Elliott 1 , Animesh D. Pardanani 1 , Naseema Gangat 1 , Abhishek A. Mangaonkar 1 , Rhett P. Ketterling 2 , Ayalew Tefferi 1 , Eric Solary 3,4 and Mrinal M. Patnaik 1 Dear Editor, Chronic myelomonocytic leukemia (CMML) is a clonal myeloid disorder characterized by peripheral blood (PB) monocytosis (absolute monocyte count (AMC) ≥1 × 10 9 /L and ≥10% of the total white blood cell count (WBC)) and overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms (MPN) 1 . Sustained PB monocytosis is a hallmark of CMML, with a mutational signature consisting of biallelic TET2, or TET2 and SRSF2 co-mutations, biasing hematopoiesis toward monocytosis 2 .…”