Biomedical Engineering Reference
In-Depth Information
A. SKIN CELL LINEAGE AND SKIN CANCERS
B. GERM CELL LINEAGE AND GERM CELL TUMORS
HAIR FOLLICLE
BULGE CELLS
505*105&/5
NEOPLASTIC
GERM CELL
EMBRYONAL
CARCINOMA
Stratum Germinativum
BASAL CELLS
SEMINOMA
Stratum Spinosum
SPERMATOCYTIC
SEMINOMA
OLIGOPOTENT
Stratum Granulosum
TRICHOEPITHELIOMA
MIXED TUMORS
Stratum
Corneum
BIPOTENT
TERATOCARCINOMA
BASAL CELL
CARCINOMA
UNIPOTENT
PAPILLOMAS
SQUAMOUS CELL
CARCINOMA
TERMINALLY
DIFFERENTIATED
KERATINIZED
CHORIOCARCINOMA
YOLK SAC CARCINOMA
TERATOMA
C. LIVER CELL LINEAGE AND LIVER CANCERS
D. MYELOID CELL LINEAGE AND MYELOID LEUKEMIA
PLURIPOTENT BONE MARROW STEM CELL
&.#3:0/"-
45&.$&--
INFANT
LIVER
STEM CELL
PERIDUCTAL OR DUCTAL
ADULT LIVER
PROGENITOR
CELL
HEMATOPOIETIC STEM CELL
MYELOID STEM CELL (HEMOCYTOBLAST)
PROMYELOCYTE
HEPATOCYTE
MYELOCYTE
POLYMORPHS
TERATOCARCINOMA
IL-3R Activation
FLT3 mutation
ACUTE MYELOID
LEUKEMIA
FLT3 inhibitors
HEPATOBLASTOMA
T15:17
PML/RAR
α
ACUTE
PROMYELOID
LEUKEMIA
Retinoic Acid
T9:22
bcr/abl
CHRONIC MYELOID
LEUKEMIA
Gleevec
CHOLANGIO-
CARCINOMA
MIXED
CHOLANGIO
HEPATOMA
HEPATOCELLULAR
CARCINOMA (HEPATOMA)
Fig. 2 Selected cell lineages and stage of maturation arrest for various cancers. A Skin cell
lineage and skin cancers. The type of skin cancer is related to the stage of differentiation at which
a block inmaturation occurs. The vertical lines indicate a block inmaturation. If the block takes
place at the level of the stem cells in the bulge of the hair follicle, mixed tumors of hair follicle,
sweat gland, and sebaceous gland elements will form; if the block occurs at the level of the basal
stem cell, basal or squamous cell cancers form; if the block is at the level of the stratum
spinosum, benign papillomas form. B Germ cell lineage and germ cell tumors. The figure
depicts the stages of maturation of germ cells at which maturation arrest produces various
tumors of the germ cell lineage. Embryonal carcinoma is a tumor of the totipotent embryonal
stem cells. From these are derived tumors that contain elements of embryonal carcinoma,
including choriocarcinoma (placenta), yolk sac tumors, and teratocarcinomas. Teratomas are
benign tumors of mixed mature cells. Seminomas are tumors expressing the spermatocytic
lineage of germinal cells. C Liver cell lineage and liver cancers. Depicted is a lineage of cells:
embryonal stem cells, infant liver cells, adult liver progenitor cells, and hepatocytes. Maturation
arrest at the embryonal cell level produces embryonal cell carcinomas or teratocarcinomas.
Hepatoblastomas occur only in children under the age of 4-5 years and are considered to arise
from a hepatic progenitor cell that disappears after this age. In the adult, liver tumors of bile
duct cells (cholangiocarcinomas) and hepatocellular carcinomas arise from a ''bipolar'' pro-
genitor cell in the adult liver. Hepatocellular cancinomas can also arise from mature hepato-
cytes, since there are essentially no terminally differentiated cells in the hepatocytic lineage.
From Sell (2006b). D Gene translocations, levels of maturation arrest, and differentiation
therapy of selected human leukemias. Specific gene translocations lead to expression of signal-
ing molecules that constitutively activate cells at various stages of differentiation in the myeloid
lineage: chronic myeloid leukemia (t9:22, Philadelphia chromosome; bcr-abl); acute promyeloid
leukemia (t15:17, PML/retinoic acid receptor); acute myeloid leukemia (multiple possibilities
including using both an activation signal (such as activation of the IL-3 receptor) and a block in
apoptosis). CML is effectively treated by Gleevec, which specifically blocks the bcr-abl tyrosine
kinase. APL is treated by retinoic acid, which reacts with the retinoic acid in the fusion product
and allows the affected cells to differentiate. Treatment of AML by differentiation therapy is
still in the experimental stage. From Sell (2005)
