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Lecture 14

PATH 310 Lecture Notes - Lecture 14: Mesylate, Protein Dimer, Intrinsically Disordered Proteins

Pathology and Molecular Medicine
Course Code
PATH 310
Christine Hough

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Chronic Myelogenous Leukemia (CML)
Neoplasia: Defining Characteristics
Abnormal mass of tissue, the growth of which:
1. Exceeds that of normal tissue of origin
2. Is autonomous; it persists despite termination of causative stimuli
grows without stimuli
Autonomous growth caused by heritable (by cells) genetic alterations (often
mutations) mutations acquired by cells
Monoclonality: all tumor cells are direct descendants of a single cell
Normal Granulocyte and Lymphocyte
Blood sample
Neutrophil: has granules in cytoplasm, myeloid cell
Lymphocyte: smaller, round, not much cytoplasm, lymphoid cell
Hematopoiesis: the formation of blood cells
All blood and immune cells formed
This process occurs in the bone marrow
Horizontal axis: maturity
HSC: least mature cell
Vertical axis: different cell lineages
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Key points in relation to hematopoiesis:
Normal adult hematopoiesis takes place in the bone marrow.
Hematopoietic stem cells: are present in small numbers, divide infrequently, are
capable of self-renewal (can generate another HSC), and are multipotent in that
they can give rise to all hematopoietic cell lineages.
Committed progenitors (myeloid, lymphoid): have lost both self-renewal
capability and multipotency, may be very proliferative, and give rise to cells in
one or a few hematopoietic lineages.
Differentiated cells: have acquired the attributes of mature, functional blood or
immune cells and are released from the bone marrow into the periphery.
A fundamental division between hematopoietic lineages is between lymphoid
and myeloid cells.
Chronic Myelogenous Leukemia (CML)
CML is usually diagnosed in adults but can occur at any age.
"Chronic phase" CML is often asymptomatic and generally manifests as an
excessive number of myeloid cells of varying degrees of maturity (i.e., mature
cells are present) in the peripheral blood. This phase generally lasts about 3 or a
few more years.
When present, symptoms include fatigue, weight loss, low hemoglobin or red
blood cell count (anemia), night sweats and a sensation of abdominal
heaiess due to a elarged splee spleoegaly.
Left untreated, chronic phase CML always transforms into acute leukemia. This
transformation is called "blast crisis" and is a serious, generally fatal occurrence.
Chronic: not severe onset, not curable
Chronic Phase CML Peripheral Blood Sample
Granulocytes at elevated numbers
Morphological appearances that reflect different stages of cells maturity
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Chronic Phase CML vs. AML
CML: mature granulocytes, range in maturity
AML: very immature granulocytes, no range in maturity
Elevated number of myeloid cells in peripheral blood, in a range of maturation
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