Myeloid Lineage Flashcards
(147 cards)
1
Q
What is AML?
A
AML stands for Acute Myeloid Leukemia, a disease that causes an accumulation of immature white blood cells in the bone marrow and peripheral blood. This disease progresses quickly and hence the term, acute.
2
Q
What is MDS?
A
MDS stands for Myelodysplastic Syndrome and is the formation of abnormal blood cells in the bone marrow and peripheral blood
3
Q
Flt3
A
FMS Like Tyrosine Kinase 3. Between 20-30% of AML patients have mutations in Flt3.
4
Q
Flt3ITD
A
Flt3 Internal Tandem Duplication. The ITD length is between 15 to 153 nucleotides. Patients with this mutation have a far worse prognosis than the Flt3TKD mutation. Signaling pathways activated by Flt3ITD are PI3 Kinase pathway, MAP Kinase pathway and the STAT5 pathway.
5
Q
Flt3TKD
A
Flt3 Tyrosine Kinase Domain. This is the active site of the Flt3 receptor and point mutations usually occur here. Signaling pathways activated by Flt3TKD are the PI3 Kinase pathway and the MAP Kinase pathway.
6
Q
APL
A
Acute Promyelocytic Leukemia. This is a leukemia like disease that sometimes precedes AML. It can be treated with ATRA and/or arsenic oxide.
7
Q
Genes frequently mutated in AML
A
Flt3, IDH1/2, NPM1, DNMT3A, CEBP alpha
8
Q
IDH1/2
A
Isocitrate Dehydrogenase 1/2. Involved in formation of alpha ketoglutarate from isocitrate in the TCA cycle. IDH1 is active in the cytosol and IDH2 is active in the mitochondria.
9
Q
IDH2 mutant
A
This mutant causes the formation of 2 hydroxyglutarate and consequently results in a block in differentiation. Enasidenib, a FDA approved drug can relieve this block.
10
Q
IDH1 mutant
A
Ivosidenib can relieve the block in differentiation in this case.
11
Q
CEBP alpha
A
This is a transcription factor involved in differentiation of white blood cells and is frequently mutated in AML.
12
Q
NPM1
A
This is a protein involved in the biogenesis of ribosomes and is frequently mutated in AML. Also is a histone chaperone.
13
Q
DNMT3A
A
This is a methyltransferase protein responsible for adding methyl groups to DNA. It is frequently mutated in AML.
14
Q
FDA approved drugs for AML
A
- Midostaurin (PKC412)(Newly Diagnosed AML)
2. Gilteritinib (ASP2215)(Relapsed Refractory AML)
15
Q
FDA approved drugs for MDS
A
- Azacytidine
16
Q
Stages of treatment for AML
A
- MRD measurement
- Induction Chemotherapy
- Consolidation Chemotherapy
- MRD measurement
- Allogenic Stem Cell Transplant
17
Q
MRD
A
MRD stands for minimal residual disease and is defined as the number of leukemic cells remaining after or during treatment and is the major cause of relapse in leukemia and cancer.
18
Q
Flt3 Allelic Burden
A
This is the number of Flt3 ITD repeats in an AML patient who has a Flt3 ITD. It is the tumor burden in the AML patient. The higher the Flt3 Allelic Burden, the worse off the patient is.
19
Q
Allogenic Stem Cell Transplant
A
This is stimulation of the patient’s immune system by injection of stem cells from a suitable donor.
20
Q
Myelocyte
A
Comprises mainly of immune cells that includes red blood cells and platelets.
21
Q
CD34+ cells
A
CD34 is a 115 kDa transmembrane glycoprotein and is found in hematopoietic stem and progenitor cells.
22
Q
7 + 3 chemotherapy regimen
A
This means a duration course where there are 7 days of cytarabine in which the first 3 days are also with an anthracycline drug, which in most cases is daunorubicin (can be substituted for doxorubicin, idarubicin or mitoxantrone)
23
Q
Anthracycline
A
These are chemotherapy drugs that are also antibiotics.
24
Q
Graft vs host disease
A
This is a condition when donor bone marrow or stem cells attack the recipient’s cells.
25
Corticosteroids
These are a class of drugs that treat inflammation. They also reduce immune system activity.
26
Lenalidomide
This is a chemotherapy drug that treats MDS, multiple myeloma and mantle cell lymphoma.
27
Differentiation Syndrome
This is a phenomena seen in a subset of APL patients treated with arsenic oxide and ATRA and in AML patients treated with IDH1/2 inhibitors. Can be treated with corticosteroids.
28
Gemtuzumab Ozogamycin
Also called Mylotarg. This is a drug antibody conjugate used to treat AML.
29
Hydroxyurea
This is an anti-metabolite that slows down growth of cancer cells.
30
ECOG Performance Status
This describes the patient's level of functioning - their ability to take care of himself/herself (0 fully active, 5 death).
31
AST and ALT
Aspartate Aminotransferase and Alanine Aminotransferase denotes function of the liver.
32
Qtc prolongation
This means delayed ventricular repolarization. That means the heart takes longer to recharge between beats.
33
Basophilia
This is when there are more than 200 basophils/microliter in the venous blood.
34
Acute Leukemia
This is when blasts are more than 20% in the blood.
35
Cytopenia
This is when there is a reduction in the number of mature blood cells.
36
Aplastic Anemia
This is when the body stops producing new blood cells.
37
CD33
An antigen marker in AML cells and a target for Gemtuzumab Ozogamycin
38
Engraftment
This is when blood forming cells upon transplant start to grow and make healthy blood cells.
39
Comorbidity
The simultaneous presence of two or more diseases or medical conditions in a patient.
40
Graft vs Leukemia Effect
This is when the donor immune cells are able to eliminate recipient leukemic cells upon allo HSCT.
41
HLA Testing
This is called "Human Leukocyte Antigen Testing." It is a blood test that identifies antigens on the surface of cells and tissues of recipient patients so that a compatible donor can be assigned.
42
Umbilical cord blood
This is sometimes used in transplant since it has a lower graft vs host disease and rapid availability.
43
Cyclophosphamide
This is a chemotherapy drug used to suppress the immune system specifically allo-reactive lymphocytes.
44
Deferasirox
This is an iron chelator drug.
45
Busulfan
This is a chemotherapy drug that prepares the body for a stem cell transplant.
46
Tomotherapy
This is a radiation modality where the patient is scanned across a modulated strip-beam.
47
Cyclosporine
This is used to prevent organ rejection in people who receive liver, kidney and heart transplant. Inhibits IL2 and IL2 receptor expression activation thus preventing T cell activation.
48
Mast Cells
These are cells in tissues that are filled with basophil granules. They release histamine during an inflammatory and allergic response.
49
Mesenchymal Stem Cells
These are cells in the bone marrow and are important for making and repairing skeletal tissue such cartilage, bone and fat found in the bone marrow.
50
Muscle Satellite Cells
These multipotent cells are found in muscle and the mature cells have very little cytoplasm.
51
Haplo-Identical Transplantation
This is a half matched stem cell transplant from a family member
52
Fludarabine Melphalan Conditioning regimen
This is a conditioning regimen that uses Fludarabine for 5 days followed by a single day of Melphalan. Both these drugs are chemotherapy drugs.
53
Temozolmide
An alkylating agent, methylates the O6 residue of guanines to prevent DNA duplication during cell proliferation and induces cell death and apoptosis.
54
Cyclopamine
This is topical cream that inhibits SHH by inhibiting SMO.
55
Teratogenic
Any agent that retards the development of the fetus or embryo.
56
GDC-0449
This is a FDA approved drug that targets locally advanced and metastatic BCC.
57
p15
This is a tumor suppressor and encodes for a cyclin dependent kinase inhibitor.
58
MDM2
This is a p53 E3 Ubiquitin Ligase that causes proteolytic degradation of p53.
59
Auer Rods
These are red or pink needle shaped structures found in myeloid cells containing agglomeration of azurophillic granules.
60
ACY-957 and ACY-1035
These are HDAC inhibitors
61
Alemtuzumab
A drug that induces T cell depletion and used for treatment of CLL. Targets CD52 protein in T and B cells.
62
Etoposide
This is a drug that stops growth of cancer cells. It does this by stabilization of an enzyme cleaved DNA complex called the cleavage complex.
63
Fluconazole
A drug used to reduce the incidence of systemic and superficial fungal infections.
64
Intraconazole
A drug that has been shown to reduce mold infections.
65
Defribotide
This is a drug that causes breakdown of clots and is used to treat veno occlusive disease.
66
Defribotide
This is an injection drug given to patients with veno-occlusive disease (blockage of liver arteries).
67
Methotrexate
This is a chemotherapy drug and also an immunosuppressant used to treat leukemia and other cancers.
68
Tacrolimus
This is an immunosuppressive drug given to patients right before stem cell transplant thus preventing organ rejection.
69
Thalidomide
This is an immunomodulator drug. It can be used with dexamethasone to treat multiple myeloma.
70
Hypothyrodism
Abnormally low activity of the thyroid gland resulting in retardation of growth and mental development in children and adults.
71
Hypogonadism
Absence or reduction of hormone secretion of the gonads (testes and ovaries).
72
Allograft
A tissue graft from a donor as the same species as the recipient but not identical.
73
Deferasirox
Iron chelator drug.
74
Clofarabine
A purine analog that has anti-leukemic properties.
75
Rapamycin
This is an immunosuppressive drug that arrests cell cycle progression at G1. It is a mTOR inhibitor and produces T regulatory cells.
76
Markov model
Determination of three transplantation strategies of newly diagnosed MDS: at diagnosis, leukemia progression and the interval between diagnosis and leukemia progression.
77
Dyspnea
Difficult or labored breathing
78
Hyperkalemia
Higher than normal levels of potassium in the bloodstream.
79
Gas6
This stands for Growth Arrest Specific Gene 6 and its protein is a ligand for Axl.
80
BGB324
This is an inhibitor of Axl.
81
JQ1
This is an inhibitor of Bromodomain BRD4.
82
P300/CBP
Proteins important for hematopoietic differentiation.
83
Gfi1b
This is Growth Factor Independent protein 1B and is a transcriptional repressor.
84
MBD
These are Methyl Binding Domain proteins that attract HDAC (Histone Deacetylase) and HMT (Histone Methylase) to methylated DNA.
85
MOZ
These are HATs that have two co-activation domains and a HAT catalytic domain. Functional MOZ is required for HSC expansion. Loss of MOZ function also leads to defects in B cell development in mice. MOZ represses p16 transcription.
86
p16
This is a tumor suppressor and acts as a Cdk inhibitor.
87
5q deletion
This rare chromosomal aberration is present in AML and MDS. The fifth chromosome is missing or has been deleted. Has a good prognosis in MDS.
88
Gata1
This is a key erythroid developmental regulator.
89
Brd1-Hbo1 HAT complex
This is an important H3K14 HAT important for transcriptional activation of key erythroid regulators.
90
c-myb
c-myb with P300/CBP repress transcription of key genes involved in myeloid differentiation and thus induces transformation. This interaction is also required for AE and MLL fusion protein promoted tranformation.
91
Heparin
This is an anti-coagulant.
92
Pyrogen
This is a substance that induces fever.
93
Histamine
This is a substance that is released by basophils and promotes vasodilation and increased vascular permeability.
94
Antibodies (classes)
A, E, D, G and M.
95
Clarithromycin
This is a CYP3A4 inhibitor. CYP3A4 is produced by stromal cells and hepatic cells.
96
Enediyne
These are organic compounds that have limited use as anti-tumor antibiotics. They can cause cell apoptosis but are unable to differentiate cancer cells from healthy cells.
97
Calicheamicin
This is released from lysosomes after GO effects and binds to DNA inducing breaks causing cell apoptosis.
98
Fractionated Dosing
Using lower dosage but given more frequently in a study.
99
Inotuzumab ozogamicin
Drug antibody conjugate that targets CD22.
100
ALFA-701 Study
This study looks at gemtuzumab ozogomycin with chemotherapy for >60 yrs patients with AML (newly diagnosed).
101
Guthrie card
These are when blood spots are collected from heels of new born to screen for diseases.
102
OGG1
This stands for 8-oxoguanine DNA glycosylase. This is a DNA repair enzyme that is downregulated by functional RUNX1.
103
Deletion 9q
This is a chromosomal aberration found in a small subset of t(8;21)(RUNX1)cases.
104
TLE1 and TLE4
These are most likely tumor suppressor genes that are removed in Deletion 9q in t(8;21) cases.
105
AML1-ETO
AML1 is the RUNT homology domain and the ETO is the functional domain.
106
PU-1
This is an ETS family transcription factor that has multiple roles in hematopoiesis.
107
FAB Classification
This stands for French, American, British classification and is a system of classifying leukemia from M0 to M7. It is based on the cell from which the leukemia is derived and the level of maturity of the cell.
108
Immunophenotyping
This is a technique to study the level of protein expressed in cells.
109
Calpains
These are calcium dependent non lysosomal cysteine proteases
110
Connexin (Cx43)
These are proteins that form gap junctions and are involved in communications between cells.
111
Mastocytosis
This is when there is an excess number of mast cells in tissues.
112
Tryptase
This is a secretory granule derived serine protease contained in mast cells and is a marker for mast cell activation.
113
POUF4F1
This is a transcription factor important for embryonic brain development.
114
PRAME
This stands for preferentially expressed antigen of melanoma. The expression of this gene may be used for detection of MRD. Upregulated with t(8;21).
115
Chemosensitivity
This is a technique that measures the amount of tumor cells that are killed by chemotherapy. The test is done after the tumor cells are removed from the body.
116
CAV1
This is a structural membrane protein. Upregulated with t(8;21)
117
LCP1
This is cancer associated actin bundling protein LCP1 (Lymphocytic Cytosolic Protein 1). Downregulated with t(8;21).
118
microRNA
These are small noncoding RNAs. Most are down regulated with t(8;21).
119
Valproic Acid
This is synthetic crystalline solid with anticonvulsant properties used for the treatment of epilepsy.
120
Sca1
This stands for stem cell antigen and is a marker for hematopoietic stem cells,
121
hematocrit
The ratio of volume of red blood cells to the total volume of blood.
122
BLNK
This is a SH2 domain containing leukocyte protein.
123
signalosome
This is a large supramolecular protein complex that enhances the signaling capacity.
124
Vadastuximabe Talirine
This is a CD33 antibody conjugated to PBD used for treatment of older patients with newly diagnosed AML. This drug has been discontinued after phase 3 trials showed increased patient deaths.
125
Ac-lintuzumab
This is a drug used to target the CD33 antigen on AML cells.
126
CSL360
This is a drug that targets the CD123 antigen in AML cells.
127
SL-401
This is a recombinant immunotoxin that combines the diphtheria toxin to IL3 ligand to target the CD123 antigen.
128
Capillary Leak Syndrome
This is a phenomena sometimes seen in patients with AML treated with SL-401, when massive amounts of plasma from blood vessels leaks into neighboring muscles and body cavities.
129
Iomab-b
This is a CD45 antibody conjugated to Iodine 131 used to treat AML.
130
Fc optimized antibodies
These combine antibody mediated targeting of AML associated antigens with NK cell activation that promote antibody dependent cellular toxicity.
131
Oxidative Burst
This is a phenomena when neutrophils and monocytes release reactive oxygen species (ROS) such as hydrogen peroxide and superoxide to degrade internalized pathogens.
132
Pancytopenia
This is a condition when there is a deficiency of the three kinds of blood cells (red cells, white cells and platelets).
133
Cytidine Deaminase
This is an enzyme for metabolism of cytarabine and produced in the bone marrow stroma.
134
Clarithromycin (Biaxin)
This is a drug that targets CYP3A4 in the bone marrow microenvironment
135
Dexamethasone
This is a glucocorticoid and acts by suppressing migration of neutrophils and decreases lymphocyte colony formation.
136
Ketoconazole
This is a drug that metabolizes CYP3A4.
137
Driver Mutation
This is a mutation that gives cancer cell a fundamental growth advantage for its neoplastic transformation.
138
Passenger Mutation
These are mutations that do not alter fitness but occurred in a cell that coincidentally or subsequently acquired a driver mutation and are therefore found in every cell with that driver mutation.
139
Objective Response
This is a proportion of patients that obtain a partial or complete response to treatment.
140
Sunitinib
This is a tyrosine kinase inhibitor and a chemotherapy agent.
141
Combination Index Value
This is used to determine the degree of drug interaction.
142
Idiopathic Pneumonia Syndrome
This is a noninfectious pulmonary complication with diffuse lung injury. after HSCT.
143
Sorafenib N Oxide
This is an active metabolite of sorafenib.
144
Active metabolite
This is an active form of the drug after it has been processed by the body.
145
CXCR4 Inhibitor
This drug mobilizes the bone marrow malignant cells sensitizing them for chemotherapy.
146
Etoposide
This is a chemotherapy drug that binds to topoisomerase II and inhibits DNA synthesis.
147
ALG
Anti Lymphocyte Globulin
