Bad prognosis in AML is indicated by aEUR'
Monosomy Prognostic factors in AML Favourable prognostic factors Unourable prognostic factors Miscellaneous prognostic factors * Age < 40 yrs * del (7q) * In recent years, with availability * AML without antecedent MDS/ MPD * dui (5q) of markers on bone marrow * Blast cells with Auer rods * 11q23 - MLL +ve trephine sections, it has been * TLC < (25 x 109/L) * 3q21 possible to study antiogenesis, * t (15;17) in AML - M3- PMURARA +ve ' Expression of MDR-1 gene (Multidrug proliferative index, apoptosis and * t (8;21) in AML-M, * Inv (16) in AML- M4Eo resistance gene) * 3q26 other parameters * FAB subtype - AML- M2, M3, M4 *Complex karyotypes * High WBC count > 100 x 109/L * AML with preceeding MDS/ PMD * Extremes of age <2 years and > 55 years FLT-3 mutation * -7/7q * Extramedullary disease in AML- M5 * Presence of CNS involvement * FAB subtype AML -MO, M6, M7 -- * t (8 ; 21)Q in AML - M2 Good prognosis * Inv (16) in AML- M4 E,, * t (15 ; 17)Q in AML - M3 - PML /RAFA +ve Moderately ourable outome * No cytogenetic abnormality Q * del (7q) * Monosomy 5 or 7 * del (5q) * inv (3) (q 21. q 26) * 11(123 - MLL +ve * t (3;3) Poor prognosis * 3q21 * t (6:11) * Expression of MDR-1 gene * t (10:11) * 3q26 * t (9;22) Genetic abnormalities in normal cytogenetic AML Name Prognosis Prevalence Expression NPM-1 (nuclephosmin) Favourable 50-60% Mutation FLT3-ITD The Ems - like tyrosine kinase 3 Gene Unourable 3040% Mutation FLT3 -Asp835 Unclear 5 - 10% Mutation BAALC (Brain and acute leukemia cytoplasmic) Unourable 65.7% Over expression MNI (Meningioma I) Unourable 50% Over expression MLI -PTD (Mixed lineage leukemia) Unourable 7.7% Mutation / over expression CEBPa (CCAT/Enhancer binding protein alpha gene) Favour able 15 - 20% Mutation ERG-I (The E1S-related gene Unoruable 25% Over expression AF-lq expression Unourable 75% Over expression Nuleophosmin (NPM1) mutations The most common molecular abnormality present in -50% of AML's with normal karyotype. nK- AML constitutes -45% of AML's and conveys an "intermediate" (but heterogenous) prognosis. Exon 12 NEM] mutations (always 4bp inseions) disrupt a key regulatory region. "AML with mutated NPM (nusleophosmin) has a ourable prognosis". Loss of X.Y chromosome There is a correlation between t (8;21) and involvement of sex chromosomes (X, Y chromosomes) - Involvement of sex chromosome occur in cases with t (8;21) that may be either in the .form of loss of X chromosome or duplication of Y chromosome. - Loss of the Y chromosome or loss of the X chromosome is associated with t (8;21) in 80% to 90% cases. - But the significance of these abnormalities on prognosis is not clear. Most probably they have ourable prognosis just as t(8;21).
Monosomy
Deletion of X or Y chromosome
T (8 : 21)
Nucleophosmin mutation