American Society of Hematology

Figure 6

$Figure 6. Clonality and MDS diagnosis in AA and other refractory cytopenia. (A) Clonality (orange) is common (>50%) in AA when assessed by gene mutations and other genetic lesions, such as cytogenetic abnormalities, using advanced genomics. However, the clonal evolution does not necessarily mean the development of diseases, especially malignant ones, such as MDS. According to the current World Health Organization (WHO) criteria, patients with AA are diagnosed as having MDS when cytopenia is present and clonality is evidenced by MDS-specific cytogenetic abnormalities, such as monosomy 7, even in the absence of dysplasia or increased blast counts (pink circle). Their clone size is not relevant as long as they are found at ≥2 metaphases. On the other hand, not all clonality is associated with MDS diagnosis (and vice versa). For example, isolated abnormalities of trisomy 8, del(20q), and –Y, are not considered to be sufficient evidence of MDS diagnosis without morphological evidence or increased blast counts, because these isolated lesions may be found in normal individuals and do not likely to correlate with typical MDS pictures. Similarly, without other evidence of MDS, somatic mutations, including those affecting common targets of myeloid malignancies, are not thought to be evidence of malignant clonal evolution by themselves. In fact, in many AA cases, somatic mutations or other clonality can be compatible with normal or almost normal blood counts. By contrast, patients with unfavorable mutations (blue circle) are more likely to show poor prognosis and to satisfy the WHO criteria for MDS/AML during their clinical course than patients with other mutations. (B) A parallel relationship is also found in unexplained cytopenia in the general population. According to the WHO criteria, the clonality (cytogenetic) criteria of MDS are reserved for MDS-specific lesions, which suffice for the diagnosis of MDS, even without evidence of dysplasia or increased blast counts. Those patients with unexplained refractory cytopenia having no evidence of MDS (between red and blue circles) are designated as ICUS. Some ICUS patients show evidence of clonal evolution (CCUS), and recent reports have suggested some similarity between CCUS and MDS (see main text), for which further confirmation is needed. CCUS, clonal ICUS.$

Clonality and MDS diagnosis in AA and other refractory cytopenia. (A) Clonality (orange) is common (>50%) in AA when assessed by gene mutations and other genetic lesions, such as cytogenetic abnormalities, using advanced genomics. However, the clonal evolution does not necessarily mean the development of diseases, especially malignant ones, such as MDS. According to the current World Health Organization (WHO) criteria, patients with AA are diagnosed as having MDS when cytopenia is present and clonality is evidenced by MDS-specific cytogenetic abnormalities, such as monosomy 7, even in the absence of dysplasia or increased blast counts (pink circle). Their clone size is not relevant as long as they are found at ≥2 metaphases. On the other hand, not all clonality is associated with MDS diagnosis (and vice versa). For example, isolated abnormalities of trisomy 8, del(20q), and –Y, are not considered to be sufficient evidence of MDS diagnosis without morphological evidence or increased blast counts, because these isolated lesions may be found in normal individuals and do not likely to correlate with typical MDS pictures. Similarly, without other evidence of MDS, somatic mutations, including those affecting common targets of myeloid malignancies, are not thought to be evidence of malignant clonal evolution by themselves. In fact, in many AA cases, somatic mutations or other clonality can be compatible with normal or almost normal blood counts. By contrast, patients with unfavorable mutations (blue circle) are more likely to show poor prognosis and to satisfy the WHO criteria for MDS/AML during their clinical course than patients with other mutations. (B) A parallel relationship is also found in unexplained cytopenia in the general population. According to the WHO criteria, the clonality (cytogenetic) criteria of MDS are reserved for MDS-specific lesions, which suffice for the diagnosis of MDS, even without evidence of dysplasia or increased blast counts. Those patients with unexplained refractory cytopenia having no evidence of MDS (between red and blue circles) are designated as ICUS. Some ICUS patients show evidence of clonal evolution (CCUS), and recent reports have suggested some similarity between CCUS and MDS (see main text), for which further confirmation is needed. CCUS, clonal ICUS.

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