BCR::ABL 1 NEGATIVE MPNs Flashcards
EPIGENETIC MODIFIERS
TET2 (ten eleven translocation 2
IDH1 (isocitrate dehydrogenase 1， and IDH2
TET2 - highly mutagenic for three reasons：
all types of myeloid disorders (MPNs, MDSS, and AMLs）
in all coding regions of the gene
often biallelic （homozygous）
TP53 gene produces the_____
P53 protein
FUNCTIONS OF P53 protein
• Tumor suppressor
• controls cell cycle checkpoints and apoptosis
• loss-of-function mutations in cancers - disease progression (MPNs)
Gene that produces the protein that functions to:
TP53 gene
• Tumor suppressor
• controls cell cycle checkpoints and apoptosis
• loss-of-function mutations in cancers - disease progression (MPNs)
Absence of_______ in MPNs in the chronic phase but have been found in 20% of patients with MPNs who have progressed to AML
TP53
MUTATIONS IN SPLICING FACTORS
Mutated mRNA consequences :
longer than normal (contains additional exons or intron segments)
shorter than normal (exon splicing)
alternative exons
- results to protein products with alternative functions.
- more common in PMF than in ET or PV
Mutated mRNA
______is a tumor suppressor gene that encodes the P53 protein, a critical regulator of:
• Cell cycle checkpoints – Prevents damaged cells from dividing.
• Apoptosis (programmed cell death) – Eliminates cells with severe DNA damage.
TP53
• Absent in Chronic Phase MPNs – Most early-stage MPNs do not have ______ mutations
TP53 mutations
• Present in______ of MPNs that Progress to AML – As the disease worsens, TP53 mutations accumulate, leading to clonal evolution and resistance to therapy.
20%
> Thrombotic events are more common in…
ET and PV
> Imaging techniques
utz
computed tomography
positron emission tomography
MRI
evaluate bone marrow fat content (marker for bone marrow cellularity in PMF)
MRI
These are proteins that regulate mRNA processing, specifically the removal of introns and joining of exons to form mature mRNA.
Splicing factors
Mutations in Splicing Factors are more common in______ than in _____
Primary Myelofibrosis (PMF) than in ET or PV
______ and _____patients are at a higher risk of blood clots (thrombosis) due to excessive platelet and RBC production.
ET and PV
Imaging Techniques for Diagnosis
• – Used for detecting splenomegaly.
• – Used for evaluating extramedullary hematopoiesis.
• – Used to assess bone marrow fat content, which helps determine bone marrow cellularity in PMF patients.
Ultrasound (UTZ)
Computed Tomography (CT) and Positron Emission Tomography (PET)
Magnetic Resonance Imaging (MRI)
ET and PV
hydroxyurea
anagrelide
• ______ A myelosuppressive agent that reduces platelet and RBC production.
Hydroxyurea
• ______ Specifically used in ET to prevent vascular complications by inhibiting platelet production.
Anagrelide
Primary Myelofibrosis (PMF) Treatment
•_______ (JAK2 Inhibitor) – Targets abnormal JAK2 signaling to reduce splenomegaly and improve systemic symptoms like fatigue and night sweats.
Ruxolitinib
• Limitation: Does not eliminate the malignant clone, meaning the disease can still progress.
Therapeutic Phlebotomy (For PV)
• Goal: Maintain hematocrit below 45% in men and 42% in women to reduce thrombotic risk.
Therapeutic Phlebotomy (For PV)
