The Birth of an Army

Everything has a start right? This is indeed true for the cell types of the immune system. From the unholy trinity of the granulocytes (i.e. the neutrophils, eosinophils and basophils) to the cytotoxix  CD8+ T cells which specializes in the art of cell destruction, all these forces of death and might must have a beginning. And this beginning is of course from the haematopoietic stem cells (HSC). HSCs reside in the bone marrow and these cells can give unleash shiteload of cell types, in other words, these beasts will give birth to every single foot soldier of the immunological army under the sun. The process itself is rather complicated I have to say but the diagram below shows the birth of what is probably one of the greatest army that has graced our universe:

Colony stimulating factors

- subclass of cytokine superfamily

- protein factors able to stimulate the production of one or more colony type in semi-solid cultures of bone marrow or other haematopoietic tissue

- IL-3, IL-5, GM-CSF, Epo, Tpo, G-CSF, IL-6, LIF, OSM, M-CSF, SCF, FLT-3L

- produced by activated macrophages/T-cells and other cell types

- bind specific receptors

  -> some have receptor subunits in common

  -> stimulate signal transduction leading to transcription factor activation enhancing proliferation, viability, differentiation

Molecules, Vol. 19, Pages 14723-14781: Challenges and Opportunities of Micro#RNAs in Lymphomas

Micro#RNAs (#miRNAs) are small non-coding #RNAs that control the expression of many target messenger #RNAs (#mRNAs) involved in normal cell functions (differentiation, proliferation and apoptosis). Consequently their aberrant expression and/or functions are related to pathogenesis of many human diseases including #cancers. Haematopoiesis is a highly regulated process controlled by a complex network of molecular mechanisms that simultaneously regulate commitment, differentiation, proliferation, and apoptosis of hematopoietic stem cells (HSC). Alterations on this network could affect the normal haematopoiesis, leading to the development of haematological malignancies such as lymphomas. The incidence of lymphomas is rising and a significant proportion of patients are refractory to standard therapies. Accurate diagnosis, prognosis and therapy still require additional markers to be used for diagnostic and prognostic purpose and evaluation of clinical outcome. The dysregulated expression or function of #miRNAs in various types of lymphomas has been associated with lymphoma pathogenesis. Indeed, many recent findings suggest that almost all lymphomas seem to have a distinct and specific #miRNA profile and some #miRNAs are related to therapy resistance or have a distinct kinetics during therapy. Mi#RNAs are easily detectable in fresh or paraffin-embedded diagnostic tissue and serum where they are highly stable and quantifiable within the diagnostic laboratory at each consultation. Accordingly they could be specific biomarkers for lymphoma diagnosis, as well as useful for evaluating prognosis or disease response to the therapy, especially for evaluation of early relapse detection and for greatly assisting clinical decisions making. Here we summarize the current knowledge on the role of #miRNAs in normal and aberrant lymphopoiesis in order to highlight their clinical value as specific diagnosis and prognosis markers of lymphoid malignancies or for prediction of therapy response. Finally, we discuss their controversial therapeutic role and future applications in therapy by modulating #miRNA. #MDPI

Thrombopoietin (Tpo)

- produced by the liver and kidney, as well as striated muscle and stromal cells in the bone marrow

- production in the liver augmented by IL-6

- regulates differentiation of megakaryocytes and platelets

  -> Tpo receptor KO studies show its effects on haemopoiesis are more widespread

- negative feedback different from most hormones

  -> the effector regulates the hormone directly

  -> Tpo binds to surface of platelets, thereby reducing megakaryocyte exposure to Tpo

Erythropoietin (Epo)

- stimulates the proliferation, viability and differentiation of erythroid progenitors

- produced mainly by kidneys

- acts on bone marrow to producing more mature RBCs

- Epo used clinically to treat anaemia and in renal failure

- also used by athletes, can cause death (high haematocrits)

   -> can be detected in urine up to 3 days after doping

   -> changes in transferrin:ferritin ratios can be detected up to 3 weeks after         doping

Haematopoiesis - important diagram to understand/know

HSC = haematopoietic stem cell

CMP = common myeloid progenitor

CLP = common lymphoid progenitor

MEP = megakaryocyte-erythroid progenitor

GM = granulocyte-macrophage progenitor

TNK = T-cell - natural killer cell progenitor

BCP = B-cell precursor

MkP = megakaryocyte progenitor

EP = erythroid progenitor

MP = macrophage precursor

GP = granulocyte precursor

TP = T-cell precursor

NKP = natural killer precursor

EPO = erythropoietin

TPO = thrombopoietin

SCF = stem cell factor

GM-CSF = granulocyte-macrophage colony-stimulating factor

M-CSF = macrophage colony-stimulating factor

G-CSF = granulocyte colony-stimulating factor