HAEM5:Acute myeloid leukaemia with BCR::ABL1 fusion: Difference between revisions

The t(9:22)(q34.1;q11.2) results in the formation of the Ph chromosome and the chimeric BCR-ABL1 fusion gene. In AML, ~70 - 80% cases with ''BCR::ABL1'' harbor p210 transcripts, and 50-60% cases with additional chromosomal abnormalities<ref name=":3">{{Cite journal|last=Soupir|first=Chad P.|last2=Vergilio|first2=Jo-Anne|last3=Dal Cin|first3=Paola|last4=Muzikansky|first4=Alona|last5=Kantarjian|first5=Hagop|last6=Jones|first6=Dan|last7=Hasserjian|first7=Robert P.|date=2007-04|title=Philadelphia chromosome-positive acute myeloid leukemia: a rare aggressive leukemia with clinicopathologic features distinct from chronic myeloid leukemia in myeloid blast crisis|url=https://pubmed.ncbi.nlm.nih.gov/17369142|journal=American Journal of Clinical Pathology|volume=127|issue=4|pages=642–650|doi=10.1309/B4NVER1AJJ84CTUU|issn=0002-9173|pmid=17369142}}</ref><ref name=":4">{{Cite journal|last=Konoplev|first=Sergej|last2=Yin|first2=C. Cameron|last3=Kornblau|first3=Steven M.|last4=Kantarjian|first4=Hagop M.|last5=Konopleva|first5=Marina|last6=Andreeff|first6=Michael|last7=Lu|first7=Gary|last8=Zuo|first8=Zhuang|last9=Luthra|first9=Rajyalakshmi|date=2013-01|title=Molecular characterization of de novo Philadelphia chromosome-positive acute myeloid leukemia|url=https://pubmed.ncbi.nlm.nih.gov/22691121|journal=Leukemia & Lymphoma|volume=54|issue=1|pages=138–144|doi=10.3109/10428194.2012.701739|issn=1029-2403|pmc=3925981|pmid=22691121}}</ref><ref>{{Cite journal|last=Nacheva|first=Ellie P.|last2=Grace|first2=Colin D.|last3=Brazma|first3=Diana|last4=Gancheva|first4=Katya|last5=Howard-Reeves|first5=Julie|last6=Rai|first6=Lena|last7=Gale|first7=Rosemary E.|last8=Linch|first8=David C.|last9=Hills|first9=Robert K.|date=2013-05|title=Does BCR/ABL1 positive acute myeloid leukaemia exist?|url=https://pubmed.ncbi.nlm.nih.gov/23521501|journal=British Journal of Haematology|volume=161|issue=4|pages=541–550|doi=10.1111/bjh.12301|issn=1365-2141|pmid=23521501}}</ref><ref name=":13">{{Cite journal|last=Orsmark-Pietras|first=Christina|last2=Landberg|first2=Niklas|last3=Lorenz|first3=Fryderyk|last4=Uggla|first4=Bertil|last5=Höglund|first5=Martin|last6=Lehmann|first6=Sören|last7=Derolf|first7=Åsa|last8=Deneberg|first8=Stefan|last9=Antunovic|first9=Petar|date=2021-06|title=Clinical and genomic characterization of patients diagnosed with the provisional entity acute myeloid leukemia with BCR-ABL1, a Swedish population-based study|url=https://pubmed.ncbi.nlm.nih.gov/33433047|journal=Genes, Chromosomes & Cancer|volume=60|issue=6|pages=426–433|doi=10.1002/gcc.22936|issn=1098-2264|pmid=33433047}}</ref>.  The most common BCR-ABL1 transcripts p190 and p210 have been detected in nearly equal distribution<ref name=":2">{{Cite journal|last=Neuendorff|first=Nina Rosa|last2=Burmeister|first2=Thomas|last3=Dörken|first3=Bernd|last4=Westermann|first4=Jörg|date=2016|title=BCR-ABL-positive acute myeloid leukemia: a new entity? Analysis of clinical and molecular features|url=https://www.ncbi.nlm.nih.gov/pubmed/27297971|journal=Annals of Hematology|volume=95|issue=8|pages=1211–1221|doi=10.1007/s00277-016-2721-z|issn=1432-0584|pmid=27297971}}</ref>. Since p190 is very rare in CML (p210 transcripts in >99% of cases), the presentation with a p190 transcript is in favor of the diagnosis of AML rather than CML<ref name=":1">Arber DA, et al., (2017). Acute Myeloid Leukemia, in Hematopathology, 2nd Edition. Jaffe E, Arer DA, Campo E, Harris NL, and Quintanilla-Fend L, Editors. Elsevier:Philadelphia, PA, p817-846.</ref>.

Additional chromosomal aberrations are infrequently seen in BCR-ABL AML, it has been described together with different class II aberrations such as CBFB-MYH11, RUNX1- RUNX1T1 and PML-RARA<ref name=":12" /><ref name=":2" />. In AML, BCR-ABL1 seems to cooperate with several AML-specific aberrations such as inv(16), t(8;21) and myelodysplasia-related cytogenetic aberrations<ref name=":2" /><ref name=":12">{{Cite journal|last=Bacher|first=Ulrike|last2=Haferlach|first2=Torsten|last3=Alpermann|first3=Tamara|last4=Zenger|first4=Melanie|last5=Hochhaus|first5=Andreas|last6=Beelen|first6=Dietrich W.|last7=Uppenkamp|first7=Michael|last8=Rummel|first8=Mathias|last9=Kern|first9=Wolfgang|date=2011|title=Subclones with the t(9;22)/BCR-ABL1 rearrangement occur in AML and seem to cooperate with distinct genetic alterations|url=https://www.ncbi.nlm.nih.gov/pubmed/21275954|journal=British Journal of Haematology|volume=152|issue=6|pages=713–720|doi=10.1111/j.1365-2141.2010.08472.x|issn=1365-2141|pmid=21275954}}</ref>. (For diagnostic purpose, note that inv(16) is not restricted to AML and can also be found in CML-MBC). Additional chromosomal aberrations, such as an additional Ph chromosome, trisomy 19 and isochromosome 17q seen in CML MBP are infrequently seen in AML with ''BCR::ABL1.''<!-- how to align left???  -->

• ‐7, del(7q)<ref>{{Cite journal|last=Tirado|first=Carlos A.|last2=Valdez|first2=Federico|last3=Klesse|first3=Laura|last4=Karandikar|first4=Nitin J.|last5=Uddin|first5=Naseem|last6=Arbini|first6=Arnaldo|last7=Fustino|first7=Nicholas|last8=Collins|first8=Robert|last9=Patel|first9=Sangeeta|date=2010-07|title=Acute myeloid leukemia with inv(16) with CBFB–MYH11, 3′CBFB deletion, variant t(9;22) with BCR–ABL1, and del(7)(q22q32) in a pediatric patient: case report and literature review|url=https://doi.org/10.1016/j.cancergencyto.2010.03.001|journal=Cancer Genetics and Cytogenetics|volume=200|issue=1|pages=54–59|doi=10.1016/j.cancergencyto.2010.03.001|issn=0165-4608}}</ref>

Mutations of ''NPM1, FLT3'' or ''DNMT3A'' are not commonly detected<ref name=":13" />. Other mutated genes include ''ASXL1, BCOR, IDH1 / IDH2'' and ''SRSF2''; each of these occur in 10 - 15% of cases<ref>{{Cite journal|last=Konoplev|first=Sergej|last2=Yin|first2=C. Cameron|last3=Kornblau|first3=Steven M.|last4=Kantarjian|first4=Hagop M.|last5=Konopleva|first5=Marina|last6=Andreeff|first6=Michael|last7=Lu|first7=Gary|last8=Zuo|first8=Zhuang|last9=Luthra|first9=Rajyalakshmi|date=2013-01|title=Molecular characterization of de novo Philadelphia chromosome-positive acute myeloid leukemia|url=https://pubmed.ncbi.nlm.nih.gov/22691121|journal=Leukemia & Lymphoma|volume=54|issue=1|pages=138–144|doi=10.3109/10428194.2012.701739|issn=1029-2403|pmc=3925981|pmid=22691121}}</ref><ref>{{Cite journal|last=Eisfeld|first=A.-K.|last2=Mrózek|first2=K.|last3=Kohlschmidt|first3=J.|last4=Nicolet|first4=D.|last5=Orwick|first5=S.|last6=Walker|first6=C. J.|last7=Kroll|first7=K. W.|last8=Blachly|first8=J. S.|last9=Carroll|first9=A. J.|date=2017-10|title=The mutational oncoprint of recurrent cytogenetic abnormalities in adult patients with de novo acute myeloid leukemia|url=https://pubmed.ncbi.nlm.nih.gov/28321123|journal=Leukemia|volume=31|issue=10|pages=2211–2218|doi=10.1038/leu.2017.86|issn=1476-5551|pmc=5628133|pmid=28321123}}</ref><ref name=":13" />.

Bone marrow with myeloid blasts >20% combined with detection of t(9,22) by karyotype analysis or BCR-ABL1 using FISH or reverse transcriptase-quantitative PCR (RT-qPCR)<ref name=":2" />.  A graphic of the clinical path for the differential diagnosis of BCR-ABL1 positive acute myeloid leukemia and chronic myeloid leukemia-myeloid blast crisis (CML-MBC) is presented<ref name=":2" />.

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