HRX involvement in de nova and secondary leukemias with diverse chromosome 11q23 abnormalities

Stephen P. Hunger, Douglas C. Tkachuk, Michael D. Amylon, Michael P. Link, Andrew J. Carroll, Jeanna L. Welborn, Cheryl L. Willman, Michael L. Cleary

Research output: Contribution to journalArticle

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Abstract

Chromosome band 11q23 is a site of recurrent translocations and interstitial deletions in human leukemias. Recent studies have shown that the 11q23 gene HRX is fused to heterologous genes from chromosomes 4 or 19 after t(4;11)(q21;q23) and t(11;19)(q23;p13) translocations to create fusion genes encoding proteins with structural features of chimeric transcription factors. In this report, we show structural alterations of HRX by conventional Southern blot analyses in 26 of 27 de novo leukemias with cytogenetically diverse 11q23 abnormalities. The sole case that lacked HRX rearrangements was a t(11;17)-acute myeloid leukemia with French-American-British M3-like morphology. We also analyzed 10 secondary leukemias that arose after therapy with topoisomerase II inhibitors and found HRX rearrangements in 7 of 7 with 11q23 translocations, and in 2 of 2 with unsuccessful karyotypes. In total, we observed HRX rearrangements in 35 leukemias involving at least nine distinct donor loci (1q32, 4q21, 6q27, 7p15, 9p21-24, 15q15, 16p13, and two 19p13 sites). All breakpoints localized to an 8-kb region that encompassed exons 5-11 of HRX, suggesting that fusion proteins containing similar portions of HRX may be consistently created in leukemias with 11q23 abnormalities. We conclude that alteration of HRX is a recurrent pathogenetic event in leukemias with 11q23 aberrations involving many potential partners in a variety of settings including acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia in blast crisis, and topoisomerase II inhibitor-induced secondary leukemias of both the myeloid and lymphoid lineages.

Original languageEnglish (US)
Pages (from-to)3197-3203
Number of pages7
JournalBlood
Volume81
Issue number12
StatePublished - Jun 15 1993

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Topoisomerase II Inhibitors
Chromosomes
Chromosome Aberrations
Leukemia
Fusion reactions
Genes
Gene encoding
Aberrations
Exons
Proteins
Transcription Factors
Acute Myeloid Leukemia
Blast Crisis
Lymphoid Leukemia
Chromosomes, Human, Pair 19
Chromosomes, Human, Pair 4
Myeloid Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Southern Blotting
Karyotype

ASJC Scopus subject areas

  • Hematology

Cite this

Hunger, S. P., Tkachuk, D. C., Amylon, M. D., Link, M. P., Carroll, A. J., Welborn, J. L., ... Cleary, M. L. (1993). HRX involvement in de nova and secondary leukemias with diverse chromosome 11q23 abnormalities. Blood, 81(12), 3197-3203.

HRX involvement in de nova and secondary leukemias with diverse chromosome 11q23 abnormalities. / Hunger, Stephen P.; Tkachuk, Douglas C.; Amylon, Michael D.; Link, Michael P.; Carroll, Andrew J.; Welborn, Jeanna L.; Willman, Cheryl L.; Cleary, Michael L.

In: Blood, Vol. 81, No. 12, 15.06.1993, p. 3197-3203.

Research output: Contribution to journalArticle

Hunger, SP, Tkachuk, DC, Amylon, MD, Link, MP, Carroll, AJ, Welborn, JL, Willman, CL & Cleary, ML 1993, 'HRX involvement in de nova and secondary leukemias with diverse chromosome 11q23 abnormalities', Blood, vol. 81, no. 12, pp. 3197-3203.
Hunger SP, Tkachuk DC, Amylon MD, Link MP, Carroll AJ, Welborn JL et al. HRX involvement in de nova and secondary leukemias with diverse chromosome 11q23 abnormalities. Blood. 1993 Jun 15;81(12):3197-3203.
Hunger, Stephen P. ; Tkachuk, Douglas C. ; Amylon, Michael D. ; Link, Michael P. ; Carroll, Andrew J. ; Welborn, Jeanna L. ; Willman, Cheryl L. ; Cleary, Michael L. / HRX involvement in de nova and secondary leukemias with diverse chromosome 11q23 abnormalities. In: Blood. 1993 ; Vol. 81, No. 12. pp. 3197-3203.
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abstract = "Chromosome band 11q23 is a site of recurrent translocations and interstitial deletions in human leukemias. Recent studies have shown that the 11q23 gene HRX is fused to heterologous genes from chromosomes 4 or 19 after t(4;11)(q21;q23) and t(11;19)(q23;p13) translocations to create fusion genes encoding proteins with structural features of chimeric transcription factors. In this report, we show structural alterations of HRX by conventional Southern blot analyses in 26 of 27 de novo leukemias with cytogenetically diverse 11q23 abnormalities. The sole case that lacked HRX rearrangements was a t(11;17)-acute myeloid leukemia with French-American-British M3-like morphology. We also analyzed 10 secondary leukemias that arose after therapy with topoisomerase II inhibitors and found HRX rearrangements in 7 of 7 with 11q23 translocations, and in 2 of 2 with unsuccessful karyotypes. In total, we observed HRX rearrangements in 35 leukemias involving at least nine distinct donor loci (1q32, 4q21, 6q27, 7p15, 9p21-24, 15q15, 16p13, and two 19p13 sites). All breakpoints localized to an 8-kb region that encompassed exons 5-11 of HRX, suggesting that fusion proteins containing similar portions of HRX may be consistently created in leukemias with 11q23 abnormalities. We conclude that alteration of HRX is a recurrent pathogenetic event in leukemias with 11q23 aberrations involving many potential partners in a variety of settings including acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia in blast crisis, and topoisomerase II inhibitor-induced secondary leukemias of both the myeloid and lymphoid lineages.",
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AU - Amylon, Michael D.

AU - Link, Michael P.

AU - Carroll, Andrew J.

AU - Welborn, Jeanna L.

AU - Willman, Cheryl L.

AU - Cleary, Michael L.

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N2 - Chromosome band 11q23 is a site of recurrent translocations and interstitial deletions in human leukemias. Recent studies have shown that the 11q23 gene HRX is fused to heterologous genes from chromosomes 4 or 19 after t(4;11)(q21;q23) and t(11;19)(q23;p13) translocations to create fusion genes encoding proteins with structural features of chimeric transcription factors. In this report, we show structural alterations of HRX by conventional Southern blot analyses in 26 of 27 de novo leukemias with cytogenetically diverse 11q23 abnormalities. The sole case that lacked HRX rearrangements was a t(11;17)-acute myeloid leukemia with French-American-British M3-like morphology. We also analyzed 10 secondary leukemias that arose after therapy with topoisomerase II inhibitors and found HRX rearrangements in 7 of 7 with 11q23 translocations, and in 2 of 2 with unsuccessful karyotypes. In total, we observed HRX rearrangements in 35 leukemias involving at least nine distinct donor loci (1q32, 4q21, 6q27, 7p15, 9p21-24, 15q15, 16p13, and two 19p13 sites). All breakpoints localized to an 8-kb region that encompassed exons 5-11 of HRX, suggesting that fusion proteins containing similar portions of HRX may be consistently created in leukemias with 11q23 abnormalities. We conclude that alteration of HRX is a recurrent pathogenetic event in leukemias with 11q23 aberrations involving many potential partners in a variety of settings including acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia in blast crisis, and topoisomerase II inhibitor-induced secondary leukemias of both the myeloid and lymphoid lineages.

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