Cancer Cytogenetics - Myeloid Neoplasms Flashcards
Recite the most common cytogenetic abnormalities in AML.
t(8;21) - RUNX1-RUNX1T1 inv(16) or t(16;16) - CBFB-MYH11 t(15;17) - PML-RARa t(9;11); - MLLT3-MLL(KMT2A) t(6;9) - DEK-NUP214 inv(3) or t(3;3) - MECOM-EVI1
AML with t(8;21):
- Abnormality?
- Epidemiology?
- Prognosis?
- RUNX1-RUNX1T1 (core binding factor alpha subunit)
- Found in 5% of cases, usually affecting younger patients.
- Favorable prognosis.
AML with t(8;21):
- Morphology?
- Myeloblasts have abundant basophilic cytoplasm with azurophilic granules and perinuclear hofs.
- Abnormal cells have homogensous salmon-pink cytoplasm.
- Auer rods and pseudo-Chediak-Higashi granules can be seen.
AML with inv(16) or t(16;16):
- Abnormality?
- Epidemiology?
- Prognosis?
- CBFB-MYH11 (core binding factor beta + myosin)
- Found in 5-8% of all AML cases, usually younger patients.
- Good prognosis
AML with inv(16) or t(16;16):
- Morphology?
Bone marrow shows abnormal eosinophil component (larger basophilic granules, variable number)
AML with t(15;17):
- Abnormality?
- Epidemiology?
- Prognosis?
- PML-RARa (transcription factor and retinoic acid receptor)
- 5-8% of cases, usually in “mid-life”
- Good, due to responsiveness to ATRA and arsenic trioxide.
AML with t(15;17):
- Morphology?
- Clinical presentation?
- Bilobed, dumbbell-shaped nuclei with large granules & auer rods. MPO+.
- Concern for coagulopathy / DIC; a true hematologic emergency.
What impact do CD56+ or FLT-ITD mutations have on AML with t(15;17)?
CD56 positivity is associated with bad prognosis.
FLT3-ITD mutations are common but do not seem to affect the prognosis.
AML with t(9;11):
- Abnormality?
- Epidemiology?
- Prognosis?
- MLLT3-MLL/KMT2A (histone methyltransferase)
- Seen in ~10% of pediatric AML, 2% of adult.
- Great prognosis in children, poor prognosis in adults.
AML with t(9;11):
- Morphology?
- Monoblasts and promonocytes predominate. Strongly associated with the former acute monocytic and myelomonocytic leukemias.
AML with t(6;9):
- Abnormality?
- Epidemiology?
- Prognosis?
- DEK-NUP214 (DNA coiler & nuclear pore complex)
- ~1 of AML, in both adults and children.
- Poor prognosis.
AML with t(6;9):
- Morphology?
- Clinical presentation?
- Basophilia. Can have auer rods and ringed sideroblasts.
- Usually presents with pancytopenia.
AML with inv(3) or t(3;3):
- Abnormality?
- Epidemiology?
- Prognosis?
- EV1-RPN1 (transcriptional regulator & rER membrane protein)
- 1-2% of all AML, usually in adults
- Poor prognosis
AML with inv(3) or t(3;3):
- Morphology?
- Clinical presentation?
- Atypical megakaryocytes, hypogranular neutrophils, multilineage dysplasia.
- Usually presents with anemia, less often thrombocytopenia.
Recite the most common cytogenetic abnormalities in MDS.
- Deletions of 5q, 7q, 20q, and Y.
- Additions of 8.
What cytogenetic profiles portend the best prognosis in MDS? Worst?
Best: -Y, del(5q), del (20q), and normal profile.
Worst: Complex, with 3+ abnormalities.
Describe the clinical and morphologic features of MDS with isolated del(5q).
MDS that usually occurs in older women, with erythryoid hypoplasia and sometimes increase in megakaryocytes. Good prognosis and response to lenalidomide.
What is the responsible gene loss in 5q- syndrome?
Ribosomal protein S14 (RPS14); results in abnormal erythroid and megakaryocytic differentiation.
Describe the mechanism by which lenalidomide is efficacious in treatment of MDS with del(5q).
Lenalidomide induces ubiquitination of CSNK1A1 (a casein kinase), which suffers haploinsufficiency in del(5q), resulting in deletion of the tumor cells over normal.
Describe the translocation chiefly responsible for CML.
t(9;22)(q34;q11.2); BCR-ABL1
What features are characteristic of neoplasms with rearrangements of PDGFRa/b and FGFR1?
Neoplasms arise from an aberrant tyrosine kinase with characteristic eosinophilia. Usually presents as MPN, but can also manifest as lymphoid.
