Acute Myeloid Leukemia with Recurrent Cytogenetic Abnormalities
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1 Acute Myeloid Leukemia with Recurrent Cytogenetic Abnormalities
2 Acute Myeloid Leukemia with recurrent cytogenetic Abnormalities -t(8;21)(q22;q22)(aml/eto) -inv(16) or t(16;16) -t(15;17) -11q23
3 Acute Myeloid Leukemia with recurrent cytogenetic abnormalities t(8;21)(q22;q22)
4 Acute Myeloid Leukemia with recurrent cytogenetic abnormalities t(8;21)(q22;q22) 5-12% of all AMLs, 1/3 of AML-M2 cases May present with myeloid sarcoma Bone marrow blasts may be less than 20%
5 Acute Myeloid Leukemia with recurrent cytogenetic abnormalities t(8;21)(q22;q22) Morphology Bone marrow hypercellular Blasts with or without granules Auer rods frequent Eosinophils and basophils may be increased
6 Acute Myeloid Leukemia with recurrent cytogenetic abnormalities t(8;21)(q22;q22)
7 Acute Myeloid Leukemia with recurrent cytogenetic abnormalities t(8;21)(q22;q22)
8 Acute Myeloid Leukemia with recurrent cytogenetic abnormalities t(8;21)(q22;q22)
9 Acute Myeloid Leukemia with recurrent cytogenetic abnormalities t(8;21)(q22;q22)
10 Acute Myeloid Leukemia with recurrent cytogenetic abnormalities t(8;21)(q22;q22) Immunophenotype CD13+, CD33+, MPO+ Often CD19+, CD56+, CD34+ Sometimes TdT+ (dim)
11 Acute Myeloid Leukemia with recurrent cytogenetic abnormalities t(8;21)(q22;q22)
12 Acute Myeloid Leukemia with recurrent cytogenetic abnormalities t(8;21)(q22;q22) Responds frequently to aggressive therapy (high dose of Cytarabine) High complete remission rate with long term disease-free survival
13 Acute Myeloid leukemia with inv(16)(p13q22) or t(16;16) (p13;q22); (CBFb/MYH11)
14 Acute Myeloid leukemia with inv(16)(p13q22) or t(16;16)(p13;q22); (CBFb/MYH11) Definition: AML-M4e plus chromosome abnormality (occasional cases not AML-M4e)
15 Acute Myeloid Leukemia with inv(16)(p13q22) Epidemiology: % of AML -Predominantly in younger patients, but can be at any age Clinical features: -May present with myeloid sarcoma
16 Acute Myeloid Leukemia with inv(16)(p13q22): Morphology and cytochemistry Peripheral Blood: eosinophils not increased BM: hypercellular, more than 20% blasts (may be lower than 20% in some cases) -Most striking abnormality: eosinophils: immature granules, purple-violet in color, obscure cell morphology -Auer rods may be seen -3% or more blasts with MPO+ -NSE+ -Neutrophils: sparse
17 Acute Myeloid Leukemia with inv(16)(p13q22)
18 Acute Myeloid Leukemia with inv(16)(p13q22)
19 Acute Myeloid Leukemia with inv(16)(p13q22) Immunophenotype: -Myeloid marker: CD13, CD33, MPO -Monocytic marker: CD14, CD4, CD11b, CD11c, CD64, CD36, lysozyme -May show coexpression: CD2
20 Acute Myeloid Leukemia with inv(16)(p13q22) Genetics: -CBFb: heterodimer CBFa, transcription factor, binds to DNA motif like TCR enhancer -MYH11: myosin heavy chain -Use FISH, RT-PCR to identified submicroscopic case
21 Acute Myeloid Leukemia with inv(16)(p13q22) FISH
22 Acute Myeloid leukemia with inv(16)(p13q22) Fusion on q arm(leukemogenic) 5 CBFbeta MYH Fusion on p arm MYH11 CBFbeta 3
23 Acute Myeloid Leukemia with inv(16)(p13q22) Cell origin: hematopoietic stem cells with potential to differentiate to granulocytes and monocytes Prognosis and predictive factors: Tx with Cytarabine, good response and prognosis
24 Acute promyelocytic leukemia
25 Acute promyelocytic leukemia Definition: -AML with t(15;17)(q22;q21);(pml/rara) -Variants t(v;17) -Promyelocytes predominate: hypergranular and hypogranular types
26 Acute promyelocytic leukemia Epidemiology: -5-8%AML -age: mid life Clinical features: -typical (hypergranular) and microgranular APL: both with high risk for DIC -microgranular APL: high WBC with numerous promyelocytes -Basophilic cytoplasm of APL cells in patients previously treated with ATRA (relapse)
27 Acute promyelocytic leukemia Morphology and cytochemistry -Hypergranular APL: kidney-shaped, bilobed, dense large granules; Faggot cells: bundles of Auer rods MPO: (++) -Microgranular(hypogranular): bilobed (butterfly, dumbbell) promyelocytes, MPO(++) vs (- or + in monocytes) -BM: hypercellular, abundant cytoplasm, convoluted nuclei
28 Acute promyelocytic leukemia Hypergranular Hypogranular
29 Acute Promyelocytic Leukemia Hypergranular variant Hypogranular variant
30 APL hypergranular Faggots or Sultan bodies: EM: hexagonal arrangement of tubular structures with a specific periodicity of 250 um in contrast to 6-20 laminar periodocity of other Auer rods
31 Acute promyelocytic leukemia
32 APL hypogranular
33 Acute promyelocytic leukemia Immunophenotype: CD33, homogenous, bright CD13, heterogeneous CD34(-) CD15(-) Frequent CD2 and CD9 co-expression PML Ab stain (Imunocytochemistry): nuclear multigranular vs speckled in normal promyelocytes or other blasts of AMLs
34 Acute promyelocytic leukemia Features of APL with variant translocations 1) t(11;17)(q23;q21), PLZF on chr11 Several cases reported, No Auer rods, regular nuclei, pseudo Pelger-Huet, Resistant to ATRA 2) t(5;17)(q23;q12), NPM on chr 5 rare, atypical APL, no Auer rods, respond to ATRA 3) t(11;17)(q13;q21), NuMA on chr 11
35 Acute promyelocytic leukemia Genetics: FISH
36 Acute promyelocytic leukemia Cell of origin: Myeloid stem cell with potential to differentiate to granulocytic lineage Prognosis: Favorable Use of retinoids in combinatorial protocols with anthracycline-based chemotherapy for front line treatment currently results in long-term survival and potential cure in at least 60%of newly diagnosed patients.
37 Acute myeloid leukemia with 11q23(MLL) abnormalities
38 Acute myeloid leukemia with 11q23(MLL) abnormalities Definition: AML, monocytic myelomonocytic feature (M4, M5), occasional M1, M2 Epidemiology: 5-6% of AML, more in children Two clinical groups: -infants -therapy-related, topoisomerase II inhibitors (translocation of chromosome 11 and 4, 9, or 19)
39 Acute myeloid leukemia with 11q23(MLL) abnormalities Clincal Features: May present with -DIC -myeloid sarcoma (tissue infiltration: gingiva, skin)
40 Acute myeloid leukemia with 11q23(MLL) abnormalities Morphology and cytochemistry: NSE(++), MPO(-) (1) monoblasts: large abundant basophilic cytoplasm pseudopods round nuclei lacy chromatin 1-2 nucleoli (2) promonocytes: cytoplasmic granules, vacuoles nuclear folds
41 Acute myeloid leukemia with 11q23(MLL) abnormalities Monoblasts NSE
42 Acute myeloid leukemia with 11q23(MLL) abnormalities Monoblasts and promonocytes NSE
43 Acute myeloid leukemia with 11q23(MLL) abnormalities Immunophenotype: -Myeloid: CD13, CD33(+) -Monocytic: CD14, CD4, CD11b, CD11c, CD64, CD36, Lysozyme(+) -CD34(-)
44 Acute myeloid leukemia with 11q23(MLL) abnormalities Genetics: Human homolog of Drosophila trithorax gene, develop regulator HRX (MLL) at band 11q23-30 different partners for 11q, most common: chromosome 9, 19 in pediatric AML, partial tandem duplication of MLL in some AML
45 Acute myeloid leukemia with 11q23(MLL) abnormalities Cell origin: hematopoietic stem cell with multilineage potential Prognosis: intermediate survival
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