Leukocyte Disorders Etiology Flashcards
ALL - Acute Lymphoblastic Leukemia
- lymphoblast cell mutation results in:
- rapid cell proliferation/self-renewal
- reduction in normal cell proliferation
- block in cell differentiation
- increase resistance in cell apoptosis
Accumulation of abnormal lymphoblasts in the BM suppress normal hematopoiesis resulting in anemia, thrombocytopenia, and neutropenia
These abnormal lymphoblasts accumulate in other organs, primary lymphatic tissues (meninges, gonads, thymus, liver, spleen, and lymph nodes)
Only 5% are linked to genetics
Environmental agents linked to increased risk
In utero radiation exposure
Chemicals - pre/postnatal exposure (questionable)
pesticides, tobacco, alcohol, nitrites, chemotherapy
High birth weight/big baby - increased insulin-like growth factor (IGF - 1)
Lack of exposure to infections/no touchie my baby in the first few weeks/months of life¹
Acute Lymphoblastic Leukemia ALL Epidemiology
MC in children - can occur at any age
MC malignancy dx before 15 y/o
MC in ages < 5 y/o and >60 y/o
Most deaths from ALL occur in old adults
Slightly more common in males
Caucasian > African Americans
60 yo Caucasian Male, non malignant but dies
4 yo Caucasian Male, malignant, doesn’t die
Chronic Lymphocytic Leukemia CLL Etiology
a malignant lymphoid neoplasm that is characterized by the accumulation of long-lived, functionally incompetent, small mature B cells
dysfunction in the maturation of the B-cell
results in B-cells that are unable to respond to immunologic stimulation
-Exact cause is unknown
-Possible genetic predisposition
CLL Epidemiology
MC form of leukemia in the US
MC in elderly
90% occur after age 50; median age of onset is 72 y/o
Frequency
Caucasian > African American
Male > Female
72 y/o Caucasian Male living in the US
Keeping an eye out on cell lines for patients after 50 y o
Acute Myelogenous Leukemia AML Etiology
A malignant disease of the bone marrow resulting from an arrest in the early development of myeloid precursors
Pathophysiology
rapid proliferation of myeloblast without differentiation into mature cells
abnormal myeloblasts are resistant to apoptosis – don’t die off like cells normally do
accumulation of myeloblasts in (lymphatic tissue) marrow, blood, spleen, liver and cause disease in that tissue
reduction of normal hematopoiesis due to marrow accumulation
from chromosomal translocations and other genetic mutations
Myelodysplastic Syndrome (MDS) - MC risk factor
bone marrow disease of unknown etiology that occurs most often in older patients and manifests as progressive cytopenias that occur over months to years
Congenital/Genetic Disorders
Trisomy 21¹, Bloom’s syndrome², Fanconi anemia³-don’t memorize
Environmental Exposures
radiation, smoking, benzene⁴, soot, creosote, inks, dyes, tanning solution, coal dust
Chemotherapeutic agents
lose MEN. + B
Acute Myelogenous Leukemia (AML) Epidemiology
median age of onset is 70 y/o
more common in Caucasians, men and developed countries
70 y/o Caucasion male in a developed country
Chronic Myeloid Leukemia CML Etiology
A disorder characterized by dysregulated production and uncontrolled proliferation of mature and maturing granulocytes with normal differentiationresults from a single specific genetic mutationtranslocation t(9:22) - Philadelphia chromosome (Hallmark)
this translocation results in a genetic defect known as bcr/abl gene or “Philadelphia chromosome CML”
bcr/abl gene produces a protein that possess overactive tyrosine kinase (TK) activity ¹
TK is responsible for the increased cell growth, differentiation, metabolism and apoptosis
Unknown other than an increased risk with exposure to ionizing radiation (peak at 5-10 years after exposure of large dose of radiation)
3 phases of disease
First phase: chronic - WBC’s differentiate
85% of diagnoses made in chronic phase are found incidentally
patients often remain in chronic phase for 3-5 years if left untreated
Second phase: accelerated - additional cytogenetic abnormalities occur
Third “blast” phase: terminal blast crisis - immature myeloblasts rapidly proliferate (fatal)
Chronic Myeloid Leukemia CML Epidemiology
average age at presentation is 55 y/o - “middle-aged”
55 in philly
Multiple Myeloma MM
a neoplastic proliferation of plasma cells producing an overproduction of nonfunctional monoclonal immunoglobulins¹
Pathogenesis
Multiple Myeloma is preceded by a premalignant plasma cell proliferative disorder known as Monoclonal Gammopathy of Undetermined Significance (MGUS)²
MGUS results from an abnormal plasma cell response to antigenic stimulation
Proliferation of neoplastic plasma cells in the bone marrow results in diminished hematopoiesis
Neoplastic plasma cells are monoclonal resulting in a lack of adequate immunoglobulin response to infection
Neoplastic plasma cells increase osteoclastic¹ activity, hypercalcemia and bone tumor formation
Neoplastic plasma cells secrete an antibody called myeloma proteins² which are harmful to the kidneys, nerves and other organs
Infiltration of plasma cells in tissues leading to plasmacytomas³
MM Multiple Myeloma epidemiology
RI
median age of onset 65 years
M>F
African American > Caucasian/Hispanics > Asian/Pacific Islanders
RI: older age, immunosuppression, and environmental exposures
radiation, benzene¹, organic solvents, herbicides, and insecticides
65 y/o AA male who works as a farmer, or a chemical plant
