t(8;21)(q22;q22)

	t(8;21)(q22;q22) G- banding (left) - Courtesy Jean-Luc Lai and Alain Vanderhaegen (top) and Diane H. Norback, Eric B. Johnson, Sara Morrison-Delap http://www.slh.wisc.edu/cytogenetics (middle and below); R- banding (middle) - above: Jean Loup Huret; 2nd row: - Courtesy Christiane Charrin; 3rd and 4th row: - Courtesy Roland Berger. Right: FISH - Courtesy Hossein Mossafa.

Disease	ANLL
Phenotype / cell stem origin	M2 mostly, rarely: M1 or M4
Epidemiology	annual incidence: 1/106; 10% of ANLL, 40% of M2 ANLL; the most frequent anomaly in chilhood ANLL; seen in children and adults: mean age 30yrs, rare in elderly patients; male excess (4M/3F) is much less than sometimes claimed
Clinics	chloromas
Cytology	numerous and thin Auer rods; eosinophilia of the bone marrow; CD19 (early B) and CD56 (natural killer) may be expressed: the cell involved may be an early progenitor
	Translocation t(8;21) is found in 5-12% of AML. Among the non-random chromosomal aberrations observed in AML, t(8;21)(q22;q22) is one of the best known and usually correlates with AML M2, with well defined and specific morphological features. The common morphological features include the presence of large blast cells with abundant basophilic cytoplasm, often containing numerous azurophilic granulations; few blasts in some cases show very large granules (pseudo-Chediak-Higashi granules), suggesting abnormal fusion. Auer rods are frequently found. In addition to the large blast cells, there are also some smaller blasts, predominantly found in the peripheral blood. Promyelocytes, myelocytes and mature granulocytes with variable dysplasia are seen in the bone marrow. These cells may show abnormal nuclear segmentation and/or cytoplasmic staining defects including homogeneous pink colored cytoplasm - Courtesy Georges Flandrin.
Prognosis	CR in most cases (90%); but relapse is frequent, and median survival -1.5yrs (adults) to 2yrs (children)- in the range with other ANLL in some series, relatively long median survival, especially in the adults for others; no adverse effect of additional chromosome anomalies

	t(8;21)(q22;q22) : cohybridization experiments using dJ155L8 (ETO) and dJ1107L6 (AML1); note the splitting of AML1 and colocalization on der(8) with ETO - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Cytogenetics Molecular	cases with cryptic molecular translocation have been detected (similar to Ph negative CML with positive BCR-ABL) --> FISH use may be relevant
Additional anomalies	sole anomaly in only 20%; additional anomalies: numerical in 2/3, structural in 1/3; loss of Y or X chromosome in half cases (1 X must be present), del(7q) or -7, +8, del (9q): 10% each.
Variants	complex t(8;21;Var) involving a (variable) third chromosome have been described in 3%; part from chromosome 21 goes on der(8), part of the 8 on der (Var), and part of Var on der(21); therefore, the crucial event lies on der(8).

	RUNX1 (AML1) and RUNX1T1 (ETO) breakpoints in the t(8;21) / 5' RUNX1 - 3' RUNX1T1 fusion gene, and FISH - Courtesy Hossein Mossafa.
Description	5' AML1 - 3' ETO; breakpoints: at the very 5' end of ETO, between exons 5 and 6 in AML1
Detection	RT-PCR in cases: 1- of typical cell morphology, but apparently without the t(8;21); 2- for minimal residual disease detection

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