Haem-onc Flashcards
Myeloma: prognostic results:
- age
- PS
- beta2 microglobulin
- Albumin
- creatinine
- Ca
- LDH
- CRP
- BMAT % plasma cells
- cytogenetics/FISH
- gene expression profile
Myeloma:adverse cytogenetic
T(4;14) T(14;16) T(14;20) 17p- 1p- 1q+
Syndromes increased risk of acute leukaemia.
Blooms Fanconi anaemia Ataxia telangiextasia Neurofibromatosis Klinefelters Wiskott aldrich
What is MLL gene
11q23
Chemical exposure leading to AML or myelodysplasia
Benzene
Chlorambucil
Melphalan
(+RT)
Viruses associated with cancer
HTLV1 —> T cell Leukaemia/lymphoma
EBV - Burkitts and PTLD AND hodgkins
HHV8 Kaposi sarcoma and primary effusion lymphoma
HIV - lymphoma in unusual site eg CNS. Likely high grade
Myeloid cell markers
CD13
CD33
CD 117
Stem cell markers
CD34
TdT defines lymphoid lineage
T-ALL cell/immunological markers
CD7
cCD3
CD2
B All cell surface markers
CD10,
CD19
cCD22 (cytoplasmic)
AML favourable cytogenetic
t(15;17)
t(08;21)
Inv (16)
AML unfavourable cytogenetic
Del 5 or 7
Tp53 mutation
Complex rearrangements
AML molecular genetics favourable
NPM1
CEBPA (Biallelic)
T(8;21) RUNX1-RUNX1T1
Inv(16) core binding factor-myh11
Intermediate risk
NPM1 with FLT3 normal karyotype
WT NPM1 without FLT3
Other cytogenetic abnormality
High risk Complex karyotype Inv(3) -5 (del 5q) -7 (del7p) WT NPM1 With FLT3 TP53 RUNX1
AML Unfavourable molecular genetics
Complex karyotype (>4 abnormality) Inv(3) -5 (del 5q) -7 (del7p) WT NPM1 With FLT3 TP53 RUNX1 MLL
APML genetics
T(15;17) PML RAR alpha
AML subtypes 2016 WHO classification
1AML with recurrent genetic abN
- AML with myelodysplasia features
- Therapy related AML
- Myeloid sarcoma
- Myeloid associated with Downs
- AML NOS
AML precursor cells
CD34 Cd38 Cd117 Cd133 HLA DR+
AML granulocyte cell surface markers
CD13 Cd15 Cd16 CD33 Cd65 cMPO
AML monocytes cell surface markers
NSE Cd11 Cd14 Cd64 Lysozyme Cd4 Cd11b Cd36
AML megakaryocytes cell surface markers
Cd41
Cd61
Cd42
AML erythroid cell surface markers
Cd235a
Mechanism of imatinib, dasatinib, nilotinib and posatinib.
Liver - P450 cytochrome CYP3A4
Induced by ketoconazole, itraconazole,erythromycin,clarithromycin.
Inhibited by Dex, phenytoin,carbamazepine, rifampacin, St. John’s wort)
Cf warfarin CYP2C9
Closely monitor INR & thyroid
Blood film features of dysplasia:
Red cell anisocytosis, poikilocytosis, basophilic stippling
Myeloid nuclear hypolobulation, pseudo Pelger Huet, hypogranulation
Myeloblasts
Platelet anisocytosis
BMAT features of dysplasia
Erythroid binuclearity, internuclear bridging, irreg nuclear edge, megaloblastoid changes, ring sideroblasts, cytoplasmic inclusions, cytoplasmic bridging, incomplete haemoglobinisation, fringed cytoplasm or vacuolisation.
Myeloid bizarre nuclear shapes, pseudo pelger huet, nuclear hypersegmentation, Chédiak–Higashi granules, cytoplasmic hypogranulation, anisocytosis
Megakaryocytes - large monolobular forms, small binuclear forms, micromega, degranulation
Excess myeloblasts
Diagnostic = pseudo pelger huet and micro mega
Iron: >5 siderotic granules 1/3 nuclear circumference in >15% erythroid cells.
Recurrent chromosomal abnormalities presumptive diagnosis of MDS
-5 del5q
-7 del7q
i(17q) t(17p)
Del of 11q 12p 13q
Commonly mutated genes in MDS
SF3B1 TET2 RUNX1 ASXL1 SRSF2 TP53 NRAS KRAS U2AF1
Syndromes assoc with a plastic anaemia
Schwann diamond (pancreatic insuff)
Fanconi anaemia (short, pigmentation, radial Ray)
Dyskeratosis congenita (nails, leukoplakia, skin pigmentation)
TAR
DIamond Blackfan
(RSP19 gene)
Congenital amegakaryocytic thrombocytopenia
(MPL gene mutation)
Aa cytogenetic abnormality
Del 13q
Trisomy 8
Monosomy 7
Hairy cell leukaemia cell markers on flow
CD11c
CD25
CD103
CD123
3/4 distinguishes from other B LPD
Systemic mastocytosis surface markers
CD2+ CD25 mast cells
Systemic mastocystosis
KIT 816V
Diagnostic criteria of systemic mastocytosis
Major: multi focal dense infiltrates of mast cells
Minor: KIT816v point mutation
>25% Bm mast cells with abnormal morphology - spindle/atypical
CD2 or 25 on mast cells
Serum rephrase more than 20
Favourable and unfavourable markers in mantle cell lymphoma
the following features are associated with a favourable prognosis in mantle cell lymphoma (MCL): Non-nodal presentation Hypermutated IGVH Lack of genomic complexity Negative SOX11 expression
A high Ki-67 proliferation index, or p53 mutations and p16 deletions, is closely related to the more aggressive MCL subtypes, such as the blastoid variants.
Blastocyst plasmacytoid surface markers
Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) has a classical immunophenotype (CD4+/CD56+/CD123+) and dermatological manifestations.
The flow cytometry results show a mixture of positive myeloid (CD33, HLADR) and T-cell (CD2, CD4) markers. CD123 is a specific marker for BPDCN in this context.
There are negative B-cell (CD10) and monocytic (CD14 and CD64) markers. TdT, cCD3 and CD3 are all negative making acute lymphoblastic leukaemia less likely. Sezary syndrome usually shows positivity for both CD3 and CD4. Sezary cells also typically have a cerebriform nuclei morphology.
AL amyloidosis poor prognosis
Liver inv Cardiac inv MM FISH normal Autonomic neuropathy
Transient Leuk of Downs Syndrome
Immunophenotyping of the blast cells show variable expression of CD34, CD117, CD33/CD13, and platelet glycoproteins (i.e. CD36, CD42 and CD61), and aberrant expression of CD56 and CD7.
GATA1
