The New Clinicopathologic and Molecular Findings in Myeloid Neoplasms With inv(3)(q21q26)/t(3;3)(q21;q26.2)

Abstract

Context.-Inv(3)(q21q26)/t(3;3)(q21;q26.2) is the most common form of genetic abnormality of the so-called 3q21q26 syndrome. Myeloid neoplasms with 3q21q26 aberrancies include acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and blast crisis of myeloproliferative neoplasms. Recent advances on myeloid neoplasms with inv(3)/t(3;3) with regard to clinicopathologic features and novel molecular or genomic findings warrant a comprehensive review on this topic.Objective.-To review the clinicopathologic features and molecular as well as genomic alterations in myeloid neoplasms with inv(3)/t(3;3).Data Sources.-The data came from published articles in English-language literature.Conclusions.-At the clinicopathologic front, recent studies on MDS with inv(3)/t(3;3) have highlighted their overlapping clinicopathologic features with and similar overall survival to that of inv(3)/t(3;3)-harboring AML regardless of the percentage of myeloid blasts. On the molecular front, AML and MDS with inv(3)/t(3;3) exhibit gene mutations, which affect the RAS/receptor tyrosine kinase pathway. Furthermore, functional genomic studies using genomic editing and genome engineering have shown that the reallocation of the GATA2 distal hematopoietic enhancer to the proximity of the promoter of ectopic virus integration site 1 (EVI1) without the formation of a new oncogenic fusion transcript is the molecular mechanism underlying these inv(3)/t(3;3) myeloid neoplasms. Although the AML and MDS with inv(3)/t(3;3) are listed as a separate category of myeloid malignancies in the 2008 World Health Organization classification, the overlapping clinicopathologic features, similar overall survival, and identical patterns at the molecular and genomic levels between AML and MDS patients with inv(3)/t(3;3) may collectively favor a unification of AML and MDS with inv(3)/t(3;3) as AML or myeloid neoplasms with inv(3)/t(3;3) regardless of the blast count.(Arch Pathol Lab Med. 2016;140:1404-1410; doi: 10.5858/arpa.2016-0059-RA) B efore we review the recent advances of myeloid neoplasms with inv(3)(q21q26)/t(3;3)(q21;q26.2) [referred to as inv(3)/t(3;3) hereafter], the clinicopathologic features of inv(3)/t(3;3) are worth being mentioned here. The structural changes involving the long arm of chromosome 3 at bands 3q21 and 3q26.2 in the forms of inversion and translocation-namely, paracentric inversion [inv(3)(q21q26.2), referred to as inv (3) hereafter] and homologous translocations [t(3;3)(q21;q26.2), referred to as t(3;3) hereafter]-in myeloid neoplasms have long been recognized. [1][2][3][4][5] Together inv(3), t(3;3), and sometimes insertions (ins) [ins(3;3)(q26;q21q26)] or duplications (dup) [dup(3)(q21-q26)] of these chromosomal regions are collectively termed as a 3q21q26 syndrome.5 Myeloid neoplasms with 3q21q26 anomalies are not only seen in acute myeloid leukemias (AMLs), 6,7 but also in myelodysplastic syndromes (MDS) 5; blast crisis of myeloproliferative neoplasm (MPN), such as chronic myelogenous leukemia 8 or leukemic transformation of essen...

Unusual findings of acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2): A multicenter study

“…Contrast to most reports from Western countries, our patients with AML‐t(3;3)(q21;q26) are more than that of AML‐inv(3)(q21q26). This is very interesting and ethnic factors should be considered.…”

“…AML withinv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2) [inv(3)/t(3;3)] is very rare and accounts for 1%‐2% of AML . These AML cases can arise de novo or in patients with myelodysplastic syndrome (MDS), myeloproliferative neoplasms, and myelodysplastic/myeloproliferative neoplasms . It is often associated with multilineage dysplasia and a poor prognosis …”

Acute myeloid leukemia with 3q26 abnormality

“…However, this disease has been reported in mother and daughter from the same family. [ 3 ] Moreover, this pathology has also been reported from across the world,[ 1 3 4 5 ] though from this country, this is an early report.…”

“…AML with pathology of 3q26 chromosomal abnormality is one such subset of AML which is difficult to treat because the remission is short lasting spanning only few months. [ 1 ] In the current issue of the journal, three cases with this pathology have been reported. [ 2 ] The authors could get only three such cases out of 115 analyzed with karyotype over 8-year period, giving a prevalence of 2.6% which agrees well with the current literature.…”

“…[ 2 ] The authors could get only three such cases out of 115 analyzed with karyotype over 8-year period, giving a prevalence of 2.6% which agrees well with the current literature. [ 1 ] Two of the patients had this abnormality in all the chromosome plates examined, and one of the patients showed this abnormality in only one of the cells.…”