6. Cytogenetics and molecular genetics of myeloid sarcoma

Cytogenetic analysis conducted with bone marrow and peripheral blood blasts in MS patients has demonstrated cytogenetic abnormalities in more than 50% of instances [21]. Nonetheless, the rates of specific cytogenetic abnormalities associated with MS are rather diverse. Studies have elicited the frequent association of between MS and core binding factor (CBF) leukemia and AML with MLL rearrangements [22]. The most common chromosomal abnormality, t(8;21), is associated with pediatric MS or in patients with ocular involvement [21, 23, 24]. The second predominant chromosomal aberration associated with pediatric MS is inv16 [3, 25]. However, studies by Pileri et al. showed the relative rarity of t(8,21) in adult MS patients [21]. Instead, trisomy 8, monosomy 7 and MLL rearrangements constitute the majority of the cases [21]. The prevalence of inv16 was also not well documented in adult patients. In addition, other chromosomal aberrations including monosomy 5, 7 or 8 were reported in isolated cases. Nucleophosmin (NPM)-1 mutations have been reported to be in 15% of MS patients. This particular variant of MS elicits clinical attributes similar to NPM-1 positive AML and manifest primarily in M4 and M5 French American British (FAB) subclasses of AML [26]. NPM-1 mutant positive MS is also associated with the loss of CD34 expression and normal karyotype. Studies conducted by Ansari-Lari et al. have reported the presence of FLT3-ITD mutation in 33% (three of nine) of MS patients with concurrent AML [27]. However, the implications of NPM-1 and FLT3-ITD mutations on prognosis of MS are still not clear and data are too scarce for definite conclusions. In their retrospective study, Vega-Ruiz et al. showed that 3% of patients with acute promyelocytic leukemia (APL) manifest MS, predominantly in CNS [28]. Studies conducted by several groups have also attributed the development of MS to the use of all-trans retinoic acid (ATRA) or with conventional chemotherapy [29].
