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Leukemia > Myeloid Lineage > Flashcards

Myeloid Lineage Flashcards

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.

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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

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3
Q

Flt3

A

FMS Like Tyrosine Kinase 3. Between 20-30% of AML patients have mutations in Flt3.

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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.

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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.

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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.

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7
Q

Genes frequently mutated in AML

A

Flt3, IDH1/2, NPM1, DNMT3A, CEBP alpha

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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.

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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.

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10
Q

IDH1 mutant

A

Ivosidenib can relieve the block in differentiation in this case.

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11
Q

CEBP alpha

A

This is a transcription factor involved in differentiation of white blood cells and is frequently mutated in AML.

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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.

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13
Q

DNMT3A

A

This is a methyltransferase protein responsible for adding methyl groups to DNA. It is frequently mutated in AML.

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14
Q

FDA approved drugs for AML

A
  1. Midostaurin (PKC412)(Newly Diagnosed AML)

2. Gilteritinib (ASP2215)(Relapsed Refractory AML)

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15
Q

FDA approved drugs for MDS

A
  1. Azacytidine
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16
Q

Stages of treatment for AML

A
  1. MRD measurement
  2. Induction Chemotherapy
  3. Consolidation Chemotherapy
  4. MRD measurement
  5. Allogenic Stem Cell Transplant
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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.

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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.

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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.

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20
Q

Myelocyte

A

Comprises mainly of immune cells that includes red blood cells and platelets.

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21
Q

CD34+ cells

A

CD34 is a 115 kDa transmembrane glycoprotein and is found in hematopoietic stem and progenitor cells.

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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)

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23
Q

Anthracycline

A

These are chemotherapy drugs that are also antibiotics.

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24
Q

Graft vs host disease

A

This is a condition when donor bone marrow or stem cells attack the recipient’s cells.

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25
Q

Corticosteroids

A

These are a class of drugs that treat inflammation. They also reduce immune system activity.

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26
Q

Lenalidomide

A

This is a chemotherapy drug that treats MDS, multiple myeloma and mantle cell lymphoma.

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27
Q

Differentiation Syndrome

A

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.

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28
Q

Gemtuzumab Ozogamycin

A

Also called Mylotarg. This is a drug antibody conjugate used to treat AML.

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29
Q

Hydroxyurea

A

This is an anti-metabolite that slows down growth of cancer cells.

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30
Q

ECOG Performance Status

A

This describes the patient’s level of functioning - their ability to take care of himself/herself (0 fully active, 5 death).

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31
Q

AST and ALT

A

Aspartate Aminotransferase and Alanine Aminotransferase denotes function of the liver.

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32
Q

Qtc prolongation

A

This means delayed ventricular repolarization. That means the heart takes longer to recharge between beats.

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33
Q

Basophilia

A

This is when there are more than 200 basophils/microliter in the venous blood.

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34
Q

Acute Leukemia

A

This is when blasts are more than 20% in the blood.

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35
Q

Cytopenia

A

This is when there is a reduction in the number of mature blood cells.

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36
Q

Aplastic Anemia

A

This is when the body stops producing new blood cells.

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37
Q

CD33

A

An antigen marker in AML cells and a target for Gemtuzumab Ozogamycin

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38
Q

Engraftment

A

This is when blood forming cells upon transplant start to grow and make healthy blood cells.

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39
Q

Comorbidity

A

The simultaneous presence of two or more diseases or medical conditions in a patient.

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40
Q

Graft vs Leukemia Effect

A

This is when the donor immune cells are able to eliminate recipient leukemic cells upon allo HSCT.

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41
Q

HLA Testing

A

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.

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42
Q

Umbilical cord blood

A

This is sometimes used in transplant since it has a lower graft vs host disease and rapid availability.

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43
Q

Cyclophosphamide

A

This is a chemotherapy drug used to suppress the immune system specifically allo-reactive lymphocytes.

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44
Q

Deferasirox

A

This is an iron chelator drug.

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45
Q

Busulfan

A

This is a chemotherapy drug that prepares the body for a stem cell transplant.

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46
Q

Tomotherapy

A

This is a radiation modality where the patient is scanned across a modulated strip-beam.

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47
Q

Cyclosporine

A

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.

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48
Q

Mast Cells

A

These are cells in tissues that are filled with basophil granules. They release histamine during an inflammatory and allergic response.

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49
Q

Mesenchymal Stem Cells

A

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.

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50
Q

Muscle Satellite Cells

A

These multipotent cells are found in muscle and the mature cells have very little cytoplasm.

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51
Q

Haplo-Identical Transplantation

A

This is a half matched stem cell transplant from a family member

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52
Q

Fludarabine Melphalan Conditioning regimen

A

This is a conditioning regimen that uses Fludarabine for 5 days followed by a single day of Melphalan. Both these drugs are chemotherapy drugs.

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53
Q

Temozolmide

A

An alkylating agent, methylates the O6 residue of guanines to prevent DNA duplication during cell proliferation and induces cell death and apoptosis.

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54
Q

Cyclopamine

A

This is topical cream that inhibits SHH by inhibiting SMO.

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55
Q

Teratogenic

A

Any agent that retards the development of the fetus or embryo.

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56
Q

GDC-0449

A

This is a FDA approved drug that targets locally advanced and metastatic BCC.

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57
Q

p15

A

This is a tumor suppressor and encodes for a cyclin dependent kinase inhibitor.

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58
Q

MDM2

A

This is a p53 E3 Ubiquitin Ligase that causes proteolytic degradation of p53.

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59
Q

Auer Rods

A

These are red or pink needle shaped structures found in myeloid cells containing agglomeration of azurophillic granules.

60
Q

ACY-957 and ACY-1035

A

These are HDAC inhibitors

61
Q

Alemtuzumab

A

A drug that induces T cell depletion and used for treatment of CLL. Targets CD52 protein in T and B cells.

62
Q

Etoposide

A

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
Q

Fluconazole

A

A drug used to reduce the incidence of systemic and superficial fungal infections.

64
Q

Intraconazole

A

A drug that has been shown to reduce mold infections.

65
Q

Defribotide

A

This is a drug that causes breakdown of clots and is used to treat veno occlusive disease.

66
Q

Defribotide

A

This is an injection drug given to patients with veno-occlusive disease (blockage of liver arteries).

67
Q

Methotrexate

A

This is a chemotherapy drug and also an immunosuppressant used to treat leukemia and other cancers.

68
Q

Tacrolimus

A

This is an immunosuppressive drug given to patients right before stem cell transplant thus preventing organ rejection.

69
Q

Thalidomide

A

This is an immunomodulator drug. It can be used with dexamethasone to treat multiple myeloma.

70
Q

Hypothyrodism

A

Abnormally low activity of the thyroid gland resulting in retardation of growth and mental development in children and adults.

71
Q

Hypogonadism

A

Absence or reduction of hormone secretion of the gonads (testes and ovaries).

72
Q

Allograft

A

A tissue graft from a donor as the same species as the recipient but not identical.

73
Q

Deferasirox

A

Iron chelator drug.

74
Q

Clofarabine

A

A purine analog that has anti-leukemic properties.

75
Q

Rapamycin

A

This is an immunosuppressive drug that arrests cell cycle progression at G1. It is a mTOR inhibitor and produces T regulatory cells.

76
Q

Markov model

A

Determination of three transplantation strategies of newly diagnosed MDS: at diagnosis, leukemia progression and the interval between diagnosis and leukemia progression.

77
Q

Dyspnea

A

Difficult or labored breathing

78
Q

Hyperkalemia

A

Higher than normal levels of potassium in the bloodstream.

79
Q

Gas6

A

This stands for Growth Arrest Specific Gene 6 and its protein is a ligand for Axl.

80
Q

BGB324

A

This is an inhibitor of Axl.

81
Q

JQ1

A

This is an inhibitor of Bromodomain BRD4.

82
Q

P300/CBP

A

Proteins important for hematopoietic differentiation.

83
Q

Gfi1b

A

This is Growth Factor Independent protein 1B and is a transcriptional repressor.

84
Q

MBD

A

These are Methyl Binding Domain proteins that attract HDAC (Histone Deacetylase) and HMT (Histone Methylase) to methylated DNA.

85
Q

MOZ

A

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
Q

p16

A

This is a tumor suppressor and acts as a Cdk inhibitor.

87
Q

5q deletion

A

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
Q

Gata1

A

This is a key erythroid developmental regulator.

89
Q

Brd1-Hbo1 HAT complex

A

This is an important H3K14 HAT important for transcriptional activation of key erythroid regulators.

90
Q

c-myb

A

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
Q

Heparin

A

This is an anti-coagulant.

92
Q

Pyrogen

A

This is a substance that induces fever.

93
Q

Histamine

A

This is a substance that is released by basophils and promotes vasodilation and increased vascular permeability.

94
Q

Antibodies (classes)

A

A, E, D, G and M.

95
Q

Clarithromycin

A

This is a CYP3A4 inhibitor. CYP3A4 is produced by stromal cells and hepatic cells.

96
Q

Enediyne

A

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
Q

Calicheamicin

A

This is released from lysosomes after GO effects and binds to DNA inducing breaks causing cell apoptosis.

98
Q

Fractionated Dosing

A

Using lower dosage but given more frequently in a study.

99
Q

Inotuzumab ozogamicin

A

Drug antibody conjugate that targets CD22.

100
Q

ALFA-701 Study

A

This study looks at gemtuzumab ozogomycin with chemotherapy for >60 yrs patients with AML (newly diagnosed).

101
Q

Guthrie card

A

These are when blood spots are collected from heels of new born to screen for diseases.

102
Q

OGG1

A

This stands for 8-oxoguanine DNA glycosylase. This is a DNA repair enzyme that is downregulated by functional RUNX1.

103
Q

Deletion 9q

A

This is a chromosomal aberration found in a small subset of t(8;21)(RUNX1)cases.

104
Q

TLE1 and TLE4

A

These are most likely tumor suppressor genes that are removed in Deletion 9q in t(8;21) cases.

105
Q

AML1-ETO

A

AML1 is the RUNT homology domain and the ETO is the functional domain.

106
Q

PU-1

A

This is an ETS family transcription factor that has multiple roles in hematopoiesis.

107
Q

FAB Classification

A

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
Q

Immunophenotyping

A

This is a technique to study the level of protein expressed in cells.

109
Q

Calpains

A

These are calcium dependent non lysosomal cysteine proteases

110
Q

Connexin (Cx43)

A

These are proteins that form gap junctions and are involved in communications between cells.

111
Q

Mastocytosis

A

This is when there is an excess number of mast cells in tissues.

112
Q

Tryptase

A

This is a secretory granule derived serine protease contained in mast cells and is a marker for mast cell activation.

113
Q

POUF4F1

A

This is a transcription factor important for embryonic brain development.

114
Q

PRAME

A

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
Q

Chemosensitivity

A

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
Q

CAV1

A

This is a structural membrane protein. Upregulated with t(8;21)

117
Q

LCP1

A

This is cancer associated actin bundling protein LCP1 (Lymphocytic Cytosolic Protein 1). Downregulated with t(8;21).

118
Q

microRNA

A

These are small noncoding RNAs. Most are down regulated with t(8;21).

119
Q

Valproic Acid

A

This is synthetic crystalline solid with anticonvulsant properties used for the treatment of epilepsy.

120
Q

Sca1

A

This stands for stem cell antigen and is a marker for hematopoietic stem cells,

121
Q

hematocrit

A

The ratio of volume of red blood cells to the total volume of blood.

122
Q

BLNK

A

This is a SH2 domain containing leukocyte protein.

123
Q

signalosome

A

This is a large supramolecular protein complex that enhances the signaling capacity.

124
Q

Vadastuximabe Talirine

A

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
Q

Ac-lintuzumab

A

This is a drug used to target the CD33 antigen on AML cells.

126
Q

CSL360

A

This is a drug that targets the CD123 antigen in AML cells.

127
Q

SL-401

A

This is a recombinant immunotoxin that combines the diphtheria toxin to IL3 ligand to target the CD123 antigen.

128
Q

Capillary Leak Syndrome

A

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
Q

Iomab-b

A

This is a CD45 antibody conjugated to Iodine 131 used to treat AML.

130
Q

Fc optimized antibodies

A

These combine antibody mediated targeting of AML associated antigens with NK cell activation that promote antibody dependent cellular toxicity.

131
Q

Oxidative Burst

A

This is a phenomena when neutrophils and monocytes release reactive oxygen species (ROS) such as hydrogen peroxide and superoxide to degrade internalized pathogens.

132
Q

Pancytopenia

A

This is a condition when there is a deficiency of the three kinds of blood cells (red cells, white cells and platelets).

133
Q

Cytidine Deaminase

A

This is an enzyme for metabolism of cytarabine and produced in the bone marrow stroma.

134
Q

Clarithromycin (Biaxin)

A

This is a drug that targets CYP3A4 in the bone marrow microenvironment

135
Q

Dexamethasone

A

This is a glucocorticoid and acts by suppressing migration of neutrophils and decreases lymphocyte colony formation.

136
Q

Ketoconazole

A

This is a drug that metabolizes CYP3A4.

137
Q

Driver Mutation

A

This is a mutation that gives cancer cell a fundamental growth advantage for its neoplastic transformation.

138
Q

Passenger Mutation

A

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
Q

Objective Response

A

This is a proportion of patients that obtain a partial or complete response to treatment.

140
Q

Sunitinib

A

This is a tyrosine kinase inhibitor and a chemotherapy agent.

141
Q

Combination Index Value

A

This is used to determine the degree of drug interaction.

142
Q

Idiopathic Pneumonia Syndrome

A

This is a noninfectious pulmonary complication with diffuse lung injury. after HSCT.

143
Q

Sorafenib N Oxide

A

This is an active metabolite of sorafenib.

144
Q

Active metabolite

A

This is an active form of the drug after it has been processed by the body.

145
Q

CXCR4 Inhibitor

A

This drug mobilizes the bone marrow malignant cells sensitizing them for chemotherapy.

146
Q

Etoposide

A

This is a chemotherapy drug that binds to topoisomerase II and inhibits DNA synthesis.

147
Q

ALG

A

Anti Lymphocyte Globulin

Leukemia (5 decks)

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