myelodysplastic syndromes correct answers pre-leukemias; myeloid progenitor cells; cause
anemia, thrombocytopenia, and neutropenia; heterogeneous disease, but the majority are pre-
leukemic and progress to acute myeloid leukemia (AML); fatal; symptoms include hypoxia,
bleeding, and infection; caused by epigenetic abnormalities, base-pair changes, and aberrant
DNA methylation; difficult to determine how many cases exist because it is a low-risk disease
and is often asymptomatic until the late stages; age is the dominant risk factor (> 60); 20/100,000
people; exposure to radiation and alkylating agents can cause this; found through bone marrow
evaluation; usually hypercellular and dysplastic; common deletion of chromosomes 5 and 7
(monosomy); commonly more than three major genome aberrations; treatment varies and timing
is important; low risk: monitoring, blood growth cell factors, red blood cell and/or platelet
transfusions; most common are hypomethylation agents decitabine and 5-azacytidine (inhibit
DNA methyltransferase); delayed response but are standard in high risk patients; treatment is
challenging; HDAC inhibitors are in clinical trials
myeloid progenitor cells correct answers precursor cells in the bone marrow that are involved in
making mature blood cells; become leukemias and myelodysplastic syndromes
anemia correct answers abnormality in platelet count; symptom of myelodysplastic syndromes
neutropenia correct answers abnormality in the neutrophils; symptom of myelodysplastic
syndromes
normal neutrophil correct answers multilobed nucleus
abnormal neutrophils correct answers one large nucleus or two smooth, nonlobed nuclei;
hypercellular; dysplastic
hypercellular correct answers increased cellularity; symptom of myelodysplastic syndromes
,dysplasia correct answers abnormal development or growth of cells, tissues, or organs; symptom
of myelodysplastic syndromes
monosomy correct answers Chromosomal abnormality consisting of the absence of one
chromosome from the normal diploid number; commonly observed in chromosomes 5 and 7 in
myelodysplastic syndromes
revised international prognostic scoring system correct answers used to scale/score the severity
of myelodysplastic syndromes; five categories
hematopoietic stem cell transplantation (HSCT) correct answers cell in the bone marrow that
gives rise to all types of blood cells; therapy used to combat myelodysplastic syndromes; there is
a limit on how many times you can have this done because you must deplete a patient's immune
cells and replace them entirely; only curative treatment of myelodysplastic syndromes
5-azacitidine and decitabine correct answers combination therapy used to treat myelodysplastic
syndromes; target epigenetic changes; release the block on normal myeloid cell differentiation
that occurs in the cancer; hypomethylation agents; inhibit DNA methyltransferase; delayed
response but are standard in high-risk patients
lenalidomide correct answers immune therapy used to treat myelodysplastic syndromes;
derivative of flutamide; modulates how T-cells work and improve their function; amplifies T-cell
activity to boost the immune system; interferes with angiogenesis; amplifies the expression of
remaining tumor suppressor gene on chromosome 5 despite the deletion/monosomy;
immunomodulatory agent; profound response in del 5q patients; upregulates remaining tumor-
suppressor genes on 5q
chromosome 5 correct answers hotspot for tumor-suppressor genes; monosomy/deletion common
in myelodysplastic syndromes
Del 5q MDS correct answers deletion of the ribosomal subunit 14 gene that interrupts ribosomal
biosynthesis and leads to cell death; lenalidomide has a profound response in this by
upregulating remaining tumor-suppressor genes on 5q
, cutaneous T-cell lymphoma (CTCL) correct answers type of non-Hodgkin's lymphoma; derived
from T-lymphocytes; mycosis fungoides and Sézary syndrome
mycosis fungoides correct answers type of non-Hodgkin's lymphoma/cutaneous T-cell
lymphoma (CTCL); skin examination revealing rash, plaques, and tumors; frequent itching,
swollen lymph nodes, fever, chills, and sweating; most cases first seen by a dermatologist
Sézary syndrome correct answers type of non-Hodgkin's lymphoma/cutaneous T-cell lymphoma
(CTCL); very aggressive; bad prognosis (25% 5-year prognosis); erythroderma, peeling skin;
increased white blood cell count
early stage CTCL treatment correct answers topical agents: corticosteroids, chemotherapy
creams, bexarotene; phototherapy/radiation: UV light A combined with psoralen (PUVA) and UV
light B, electron beam radiation
advanced stage CTCL treatment correct answers PUVA: UV light A and psoralen;
oral/intravenous medications: bexarotene, methotrexate, HDAC inhibitor, interferon Alfa, etc.
ubiquitin-proteosome pathway correct answers the essential metabolic process of DNA repair
and protein homeostasis and degradation; certain cancers are addicted to DNA repair pathways
being out of whack; conserved pathway; polyubiquitination; 20S core (proteolytic), two 19S
regulatory; trypsin, chymotrypsin, caspase-like, and 3-25 AA peptides; E1, E2, and E3 enzymes;
76 AA; barrel-shape; 19S binding domain; 20S core; together is a 26S proteosome
DNA repair correct answers essential for genome integrity
protein synthesis and degradation correct answers important for maintaining cell division, cell
maintenance, and cell survival
synthetic lethals correct answers disabling mutation in either gene A or gene B allows survival
but disabling mutations in BOTH genes result in death; inhibition of partners is a highly targeted