intro to hematologic malignancies Flashcards
derived from cells in the bone marrow or lymphoid tissue
hematologic malignancies
Neoplastic transformation occurs when
acquired genetic alterations result in derangement of normal cell division and survival
acute leukemia arises from
immature progenitors
chronic leukemia arises from
mature/committed progenitors
factors associated with development of hematologic malignancies (4)
- genetic diseases
- chemicals/solvents
- chemo drugs
- radiation
genetic diseases associated with hema. malignancies
Down, Klinefelter, Bloom, Wiskott-Aldrich syndromes, Fanconi Anemia,
Neurofibromatosis, Ataxia Telangectasia a/w leukemia
Infections Associated with Development of Hematologic Malignancies:
African Burkitt Lymphoma, post-transplant lymphoproliferative disorders, Hodgkin lymphoma
Epstein-Barr Virus (EBV)
Infections Associated with Development of Hematologic Malignancies:
cause of adult T cell leukemia/lymphoma
Human T-Lymphotropic Virus (HTLV):
Infections Associated with Development of Hematologic Malignancies:
Kaposi’s sarcoma, primary effusion lymphoma
Human Herpes Virus 8 (HHV-8):
Infections Associated with Development of Hematologic Malignancies:
B cell lymphoma
Human Immunodeficiency Virus (HIV):
Infections Associated with Development of Hematologic Malignancies:
gastric mucosal associated lymphoid tissue (MALT) lymphoma
Helicobacter pylori
Genes that are involved with cancer development can be divided in to two groups:
- oncogenes
2. tumor suppressor genes
oncogenes result in
gain of function mutations where cells designated for apoptosis survive and proliferate
when can oncogenes occur
translocations, point mutations or duplications
Translocations often result in constitutively active________ which produce proliferation signals
tyrosine kinases
High frequency of translocations in hematologic malignancies
yep
tumor supressor genes are know as _______ and they lead to _______ mutations
they are the gate-keepers genes that regulate cell growth and lead to loss of function mutations
mutations in tumor suppressor genes often occur through ______ or ______. _____ is the most significant tumor suppressor gene
occur through point mutations or deletions
p53 is the most significant tumor suppressor gene
When tumor suppressor genes are mutated, the negative regulation or suppression is turned off leading to
uncontrolled cell growth
Blood smear
since it is easy and inexpensive to obtain and they give a lot of information of the bone marrow and lymphoid organs evaluation of the blood s,ear is often the first step in evaluation a patient with suspected hematologic disease
karyotype analysis can detect large or small defects?
they cannot detect small defects thus they usually tell is there has been a gain or loss of an entire/partial chromosome or a translocation
Uses fluorescent labeled genetic probes which hybridize to specific parts of the genome
FISH
FISH:
- can be used in both dividing- metaphase and non-dividing-interphase cells
- results:
a. 1 dot
b. 3 dots
c. fusion of 2 different colored dots
- yep
- a. 1 dot: chromosomes with deletions- monosomy
b. 3 dots: chromosomes with additions- trisomy
c. fusion of 2 different colored dots: cells with translocations
DNA polymerase enzyme synthesizes new pieces of DNA complimentary to target DNA. DNA polymerase attaches to primer and adds nucleotides amplifying target strand
PCR
PCR is used in hematologic malignancies to
demonstrate clonality in B or T lymphocytes by assessing immunoglobulin or T cell receptor rearrangement
next generation sequencing can be used to identify
drugable targets
Bioinformatics analyses are used to piece together the fragments by mapping the individual reads to the human reference genome
next generation sequencing
uses antibodies labeled with different fluorochromes which recognize the cell surface antigens
flow cytometry
Flow cytometry:
- useful how?
- fluorescence is used to
- can be used on
- labeled cells are passed through a flow cytometer where a
- normal cells have a characteristic pattern of cell surface antigens designated as a cluster of differentiation number and malignant cells often express an aberrant phenotype
- fluorescence is used to measure the cells characteristics
- can be used on blood or bone marrow
- labeled cells are passed through a flow cytometer where a laser excites emission of varying wave lengths
- Uses antibodies to stain tissue biopsies (bone marrow, lymph node)
- Tumor cells can be identified by direct visualization under the microscope
immunohistochemistry
