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Guide And Atlas For The Detection Of Minimal Residual Disease In AML

FISH Analysis and AML

FISH analysis is more sensitive than cytogenetics because a large number of cells (both interphases and metaphases) can be examined without requiring dividing cells. FISH may complement cytogenetics in establishing the presence of specific chromosomal changes, including those that are of a structural nature.[4]

M1 with trisomy 8 demonstrated by FISH

M1, acute myeloblastic leukemia. Poorly differentiated myeloblasts are present. Some contain azurophil granules, but the percentage of maturing granulocytes is less than 10%. Peroxidase stain reveals the Auer rods.[4]

FISH showing trisomy 8(+8). Shown is a FISH analysis of interphase nuclei using centromeric probes in a case of AML (M1), demonstrating trisomy 8(+8) by the presence of three green signals in one cell (leukemic) and two signals in a normal cell. The red signals are those for chromosome 7, used as an internal control.[4]

M4EO with inversion 16

M4eo, AMML, with eosinophils in marrow. Myeloblasts and monoblasts/promonocytes with eosinophils with large basophilic granules. This subtype is often associated with inv(16)(p13;q22) and a favorable prognosis, despite an increased incidence of central nervous system leukemia.[4]

Inv(16)(p13;q22). The breakpoints on this partial karyotype are indicated by arrows.[4]

CBFß-MYH11 gene involvement. Schematic presentation includes the genes involved (CBFß-MYH11). This anomaly is often associated with marrow eosinophilia and a favorable prognosis.[4]

FISH showing inv(16). A FISH analysis with a cosmid probe of a metaphase with an inv(16); the normal chromosome 16 has two signals, whereas the inverted chromosome has three signals, resulting from splitting of the gene by the break involved in the translocation.[4]

M5b with t(11q23)

M5b, acute monoblastic leukemia, more differentiated. Eighty percent or more of the myeloid marrow are monoblasts or promonocytes with at least 20% clearly recognized by the presence of twisted or folded nuclei, gray-blue cytoplasm, and scattered azurophil granules.[4]

Involvement of 11q23. Translocation involving band 11q23 in AML may occur as a result of a deletion or trans-locations with a number of other chromosomes and is usually associated with M4 or M5 and a poor prognosis.[4,16]

FEL-MLL gene involvement. A gene located at 11q23, MLL, appears to play a crucial role in the genesis of some of these types of AML.[4]

FISH showing 11q23. FISH study shown with a cosmid probe for 11q23 of a metaphase with a t(6;11) (q25;q23). In a normal cell, only two signals located on each chromosome 11 would be present. In the case shown, with t(6;11), three signals are present, due to a split of the signal on the chromosome 11 involved in the translocation.[4]

M3 Hypogranular variant of APL

FAB M3 variant. Bilobulated blasts or cells with reniform nucleus and cytoplasm with minimal to absent granules. Rare typical hypergranular cells are always located.[4]

FISH showing t(15;17). FISH study of this translocation using a cosmid probe in which the green and red signals represent the sequences in normal chromosomes 15 (green) and 17 (red); the fusion product is shown as a mixture of signals (yellow).[4]

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