Age-related clonal hematopoiesis and monoclonal B-cell lymphocytosis/chronic lymphocytic leukemia: a new association?

Condoluci, Adalgisa; Rossi, Davide

doi:10.3324/haematol.2018.191098

Cited by 7 publications

(5 citation statements)

References 18 publications

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“…Polymorphonuclear cells from the same CLL samples carried somatic mutations also present in MBL/CLL clones ( 246 ). Altogether, this supports the model of human CLL pathogenesis that begins with lymphoid clonal hematopoiesis driven by initial mutation at the stem cell level, through monoclonal B lymphocytosis, and ultimately overt CLL as a result of continuous malignant genetic evolution ( 247 ). Therefore, hematopoietic stem/progenitor cells can act as a cell-of-origin in CLL.…”

Section: Hsc and Chronic Lymphocytic Leukemiasupporting

confidence: 76%

The dark side of stemness – the role of hematopoietic stem cells in development of blood malignancies

Filipek-Gorzała,

Kwiecińska,

Szade

et al. 2024

Front. Oncol.

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Hematopoietic stem cells (HSCs) produce all blood cells throughout the life of the organism. However, the high self-renewal and longevity of HSCs predispose them to accumulate mutations. The acquired mutations drive preleukemic clonal hematopoiesis, which is frequent among elderly people. The preleukemic state, although often asymptomatic, increases the risk of blood cancers. Nevertheless, the direct role of preleukemic HSCs is well-evidenced in adult myeloid leukemia (AML), while their contribution to other hematopoietic malignancies remains less understood. Here, we review the evidence supporting the role of preleukemic HSCs in different types of blood cancers, as well as present the alternative models of malignant evolution. Finally, we discuss the clinical importance of preleukemic HSCs in choosing the therapeutic strategies and provide the perspective on further studies on biology of preleukemic HSCs.

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Section: Hsc and Chronic Lymphocytic Leukemiasupporting

confidence: 76%

The dark side of stemness – the role of hematopoietic stem cells in development of blood malignancies

Filipek-Gorzała,

Kwiecińska,

Szade

et al. 2024

Front. Oncol.

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“…This fact can be explained by the results of the deep sequencing of the genome in healthy individuals, which has revealed that as humans age, one or more hematopoietic stem and progenitor cells (HSPCs) may expand and contribute more significantly to the production of mature blood cells. This phenomenon is known as age-related clonal hematopoiesis (ARCH) and is characterized by the expansion of HSPC clones with specific genetic mutations that can increase the risk of certain diseases, such as leukemia, heart disease, and diabetes [ 50 ]. Recent research has shown that ARCH may also be associated with the expansion of B-cell clones with CLL phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…Recent research has shown that ARCH may also be associated with the expansion of B-cell clones with CLL phenotype. However, larger-scalestudies are needed to confirm this association and gain a deeper understanding of the pathogenesis of these conditions [ 50 ]. Further recent studies have shown that as individuals age, their tissues experience an increase in somatic mutations, which can lead to clonal hematopoiesis if it occurs in the hematopoietic system [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Copy Number Variations and Gene Mutations Identified by Multiplex Ligation-Dependent Probe Amplification in Romanian Chronic Lymphocytic Leukemia Patients

Balla

Tripon

Cândea

et al. 2023

JPM

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Chronic lymphocytic leukemia (CLL) is known for its wide-ranging clinical and genetic diversity. The study aimed to assess the associations between copy number variations (CNVs) and various biological and clinical features, as well as the survival rates of CLL patients and to evaluate the effectiveness of the multiplex ligation-dependent probe amplification (MLPA) technique in CLL patients.DNA was extracted from 110 patients, and MLPA was performed. Mutations in NOTCH1, SF3B1, and MYD88 were also analyzed. A total of 52 patients showed at least one CNV, 26 had at least one somatic mutation, and 10 presented both, CNVs, and somatic mutations. The most commonly identified CNVs were del(114.3), del(11q22.3), and dup(12q23.2). Other CNVs identified included del(17p13.1), del(14q32.33), dup(10q23.31), and del(19p13.2). One patient was identified with concomitant trisomy 12, 13, and 19. NOTCH1 and SF3B1 mutations were found in 13 patients each, either alone or in combination with other mutations or CNVs, while MYD88 mutation was identified in one patient. Forty-two patients had normal results. Associations between the investigated CNVs and gene mutations and patients’ overall survival were found. The presence of NOTCH1 and SF3B1 mutations or the combination of NOTCH1 mutation and CNVs significantly influenced the survival of patients with CLL. Both mutations are frequently associated with different CNVs. Del(13q) is associated with the longest survival rate, while the shortest survival is found in patients with del(17p). Even if MLPA has constraints, it may be used as the primary routine analysis in patients with CLL.

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“…This event leads to the generation of B cell subclones with different IGHV-IGHJ-IGHD rearrangements, each of which is similar to MBL. One of the MBL cells subsequently transforms into a full-blown CLL cell [246,247]. Support for this hypothesis was initially provided by the observation of an abnormal expansion of pro-B cells in the bone marrow of CLL patients.…”

Section: Origin From Hscsmentioning

confidence: 99%

Old and New Facts and Speculations on the Role of the B Cell Receptor in the Origin of Chronic Lymphocytic Leukemia

Bagnara

Mazzarello

Ghiotto

et al. 2022

IJMS

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The engagement of the B cell receptor (BcR) on the surface of leukemic cells represents a key event in chronic lymphocytic leukemia (CLL) since it can lead to the maintenance and expansion of the neoplastic clone. This notion was initially suggested by observations of the CLL BcR repertoire and of correlations existing between certain BcR features and the clinical outcomes of single patients. Based on these observations, tyrosine kinase inhibitors (TKIs), which block BcR signaling, have been introduced in therapy with the aim of inhibiting CLL cell clonal expansion and of controlling the disease. Indeed, the impressive results obtained with these compounds provided further proof of the role of BcR in CLL. In this article, the key steps that led to the determination of the role of BcR are reviewed, including the features of the CLL cell repertoire and the fine mechanisms causing BcR engagement and cell signaling. Furthermore, we discuss the biological effects of the engagement, which can lead to cell survival/proliferation or apoptosis depending on certain intrinsic cell characteristics and on signals that the micro-environment can deliver to the leukemic cells. In addition, consideration is given to alternative mechanisms promoting cell proliferation in the absence of BcR signaling, which can explain in part the incomplete effectiveness of TKI therapies. The role of the BcR in determining clonal evolution and disease progression is also described. Finally, we discuss possible models to explain the selection of a special BcR set during leukemogenesis. The BcR may deliver activation signals to the cells, which lead to their uncontrolled growth, with the possible collaboration of other still-undefined events which are capable of deregulating the normal physiological response of B cells to BcR-delivered stimuli.

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Age-related clonal hematopoiesis and monoclonal B-cell lymphocytosis/chronic lymphocytic leukemia: a new association?

Cited by 7 publications

References 18 publications

The dark side of stemness – the role of hematopoietic stem cells in development of blood malignancies

The dark side of stemness – the role of hematopoietic stem cells in development of blood malignancies

Copy Number Variations and Gene Mutations Identified by Multiplex Ligation-Dependent Probe Amplification in Romanian Chronic Lymphocytic Leukemia Patients

Old and New Facts and Speculations on the Role of the B Cell Receptor in the Origin of Chronic Lymphocytic Leukemia

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