Lucie Laplane

UMR8590 (IHPST), Université Paris I-Panthéon-Sorbonne & UMR1170, Institut de Cancérologie Gustave Roussy

The clonal evolution (CE) model and the cancer stem cell (CSC) model are two independent models of cancers, yet recent data shows intersections between the two models. This article explores the impacts of the CSC model on the CE model. I show that CSC restriction, which depends on CSC frequency in cancer cell populations and on the probability of d...

A knowledge of the historic and philosophical background gives that kind of independence from prejudices of his generation from which most scientists are suffering. This independence created by philosophical insight is—in my opinion—the mark of distinction between a mere artisan or specialist and a real seeker after truth.

The characteristic properties of stem cells – notably their ability to self-renew and to differentiate – have meant that they have traditionally been viewed as distinct from most other types of cells. However, recent research has blurred the line between stem cells and other cells by showing that the former display a range of behaviors in different...

The functional diversity of cells that compose myeloid malignancies, i.e., the respective roles of genetic and epigenetic heterogeneity in this diversity, remains poorly understood. This question is addressed in chronic myelomonocytic leukemia, a myeloid neoplasm in which clinical diversity contrasts with limited genetic heterogeneity. To generate...

Background Restorative regeneration, the capacity to reform a lost body part following amputation or injury, is an important and still poorly understood process in animals. Annelids, or segmented worms, show amazing regenerative capabilities, and as such are a crucial group to investigate. Elucidating the molecular mechanisms that underpin regenera...

Cancers rely on multiple, heterogeneous processes at different scales, pertaining to many biomedical fields. Therefore, understanding cancer is necessarily an interdisciplinary task that requires placing specialised experimental and clinical research into a broader conceptual, theoretical, and methodological framework. Without such a framework, onc...

Heterozygous mutation targeting proline 95 in Serine/Arginine-rich Splicing Factor 2 (SRSF2) is associated with V617F mutation in Janus Activated Kinase 2 (JAK2) in some myeloproliferative neoplasms (MPNs), most commonly primary myelofibrosis. To explore the interaction of Srsf2P95H with Jak2V617F, we generated Cre-inducible knock-in mice expressin...

Macrophages are widely distributed innate immune cells that play an indispensable role in a variety of physiologic and pathologic processes, including organ development, host defense, acute and chronic inflammation, solid and hematopoietic cancers. Beyond their inextricable role as conveyors of programmed cell death, we have previously highlighted...

Heterozygous mutation targeting proline 95 in Serine/Arginine-rich Splicing Factor 2 (SRSF2), associates with V617F mutation in Janus Activated Kinase 2 (JAK2) in some myeloproliferative neoplasms (MPNs), most commonly primary myelofibrosis. To explore Srsf2 P95H interaction with Jak2 V617F , we generated Cre-inducible knock-in mice expressing thes...

The presence and role of microbes in human cancers has come full circle in the last century. Tumors are no longer considered aseptic, but implications for cancer biology and oncology remain underappreciated. Opportunities to identify and build translational diagnostics, prognostics, and therapeutics that exploit cancer's second genome—the metagenom...

Background: The gain-of-function JAK2 V617F mutant is the most common driver mutation identified in myeloproliferative neoplasms (MPNs). Additional somatic variants, also found in other malignant hemopathies, are detected in primary myelofibrosis (MF) and supposed to contribute to fibrosis or leukemia development. One of these mutations affects SRS...

Acute myeloid leukemias (AML) results from the accumulation of genetic and epigenetic alterations, often in the context of an aging hematopoietic environment. The development of high-throughput sequencing—and more recently, of single-cell technologies—has shed light on the intratumoral diversity of leukemic cells. Taking AML as a model disease, we...

How flexible are cell identities? This problem has fascinated developmental biologists for several centuries and can be traced back to Abraham Trembley's pioneering manipulations of Hydra to test its regeneration abilities in the 1700s. Since the cell theory in the mid-19th century, developmental biology has been dominated by a single framework in...

Mouse models of chronic myeloid malignancies suggest that targeting mature cells of the malignant clone disrupts feedback loops that promote disease expansion. Here, we show that, in chronic myelomonocytic leukemia (CMML), monocytes that accumulate in the peripheral blood show a decreased propensity to die by apoptosis. BH3 profiling demonstrates t...

Clonal evolution, the process of expansion and diversification of mutated cells, plays an important role in cancer development, resistance and relapse. While clonal evolution is most often conceived of as driven by natural selection, recent studies uncovered that neutral evolution shapes clonal evolution in a significant proportion of solid cancers...

Somatic mutations in oncogene and tumor suppressor genes accumulate in healthy tissues throughout life and delineate clones with limited expansion. Lifestyle‐related toxic insults increase the size and number of these clones that participate to tissue ageing. Their identification has blurred the boundaries between clonal expansion and malignant tum...

In contrast to the once dominant tumour‐centric view of cancer, increasing attention is now being paid to the tumour microenvironment (TME), generally understood as the elements spatially located in the vicinity of the tumour. Thinking in terms of TME has proven extremely useful, in particular because it has helped identify and comprehend the role...

Despite the tight historical links between science and philosophy, present-day scientists often perceive philosophy as completely different from, and even antagonistic to, science. We argue here that, to the contrary, philosophy can have an important and productive impact on science. We illustrate our point with three examples taken from various fi...

The notion of tumor microenvironment (TME) has been brought to the forefront of recent scientific literature on cancer. However, there is no consensus on how to define and spatially delineate the TME. We propose that the time is ripe to go beyond an all-encompassing list of the components of the TME, and to construct a multilayered view of cancer....

What is a stem cell? Is stemness an intrinsic or extrinsic property? What role does the microenvironment play in the stemness identity? We distinguish four identities for normal and cancerous stem cells and explore their consequences for therapeutic strategy choice in the oncology setting. Acquisition of genetic and epigenetic alterations during ce...

In response to Germain (Biol Philos 27:785–810, 2012. doi:10.1007/s10539-012-9334-2) argument that evolution by natural selection has a limited explanatory power in cancer, Lean and Plutynski (Biol Philos 31:39–57, 2016. doi:10.1007/s10539-015-9511-1) have recently argued that many adaptations in cancer only make sense at the tumor level, and that...

What are leukemic stem cells (LSCs)? This is a biological, a semantic, and a philosophical question. Leukemic stem cells raise a number of questions for onco-hematologists in particular when it comes to their clinical relevance. What are their functions in the initiation and in the progression of the disease? How to identify them? How to target the...

Is it possible, and in the first place is it even desirable, to define what “development” means and to determine the scope of the field called “developmental biology”? Though these questions appeared crucial for the founders of “developmental biology” in the 1950s, there seems to be no consensus today about the need to address them. Here, in a comb...

Similar to seemingly maladaptive genes in general, the persistence of inherited cancer-causing mutant alleles in populations remains a challenging question for evolutionary biologists. In addition to traditional explanations like senescence or antagonistic pleiotropy, here we put forward a new hypothesis to explain the retention of oncogenic mutati...

The demonstration that pluripotent stem cells could be generated by somatic cell reprogramming led to wonder if these so-called induced pluripotent stem (iPS) cells would extend our investigation capabilities in the cancer research field. The first iPS cells derived from cancer cells have now revealed the benefits and potential pitfalls of this new...

abstract: Reprogramming technologies show that cellular identity can be reprogrammed, challenging the classical conception of cell differentiation as an irreversible process. If non-stem cells can be reprogrammed into stem cells, then what is it to be a stem cell, and what kind of property is stemness? This article addresses this question both phil...

The main question to which this chapter tries to answer is how can we identify theories in developmental biology? Three arguments are delivered. First, we argue that the classical conceptions of scientific theories are not adequate to the aim of identifying theories in a particular field of science. Second, we argue that a particular conception of...

This chapter brings a philosophical perspective to the concept of stem cell. Three general questions both clarify the concept of stem cell and emphasize its ambiguities: (1) How should we define stem cells? (2) What makes them different from non-stem cells? (3) What is their ontology? (i.e. what kind of property is “stemness?”) Following this last...

Like most bilaterian animals, the annelid Platynereis dumerilii generates the majority of its body axis in an anterior to posterior temporal progression with new segments added sequentially. This process relies on a posterior subterminal proliferative body region, known as the "segment addition zone" (SAZ). We explored some of the molecular and cel...

The tacit standard view that development ends once reproductive capacity is acquired (reproductive boundary, or “RB,” thesis) has recently been challenged by biologists and philosophers of biology arguing that development continues until death (death boundary, or “DB,” thesis). The relevance of these two theses is difficult to assess because the fa...

This thematic section of Biological Theory is focused on development; it raises the problem of the temporal and spatial boundaries of development. From a temporal point of view, when does development start and stop? From a spatial point of view, what is it exactly that ‘‘develops,’’ and is it possible to delineate clearly the developing entity? Thi...

Article à partir de "Jean-Jacques Kupiec, L'Origine des individus Paris, Fayard, 2008, 315 p."

The concept of CSC makes perfectly clear how researches and therapeutics strategies, while both in crisis since the 90s’, were standing on the same paradigmatic structure (the cancer cell). This concept, still restricted to the fundamental research, offers a profound theoretical renewal of the carcinogenesis. Moreover, the CSC concept is a good opp...