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

(View all pending changes)

[pending revision]

← Older edit Newer edit →

VisualWikitext

@@ Line 72: / Line 72: @@
 |''ABL1''||''BCR::ABL1''||The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.
 |t(9;22)(q34;q11.2)
-|Common (CML); Rare (AML)<ref name=":5">{{Cite journal|last=Al Hamad|first=Mohammad|date=2021|title=Contribution of BCR-ABL molecular variants and leukemic stem cells in response and resistance to tyrosine kinase inhibitors: a review|url=https://pubmed.ncbi.nlm.nih.gov/35284066|journal=F1000Research|volume=10|pages=1288|doi=10.12688/f1000research.74570.2|issn=2046-1402|pmc=8886173|pmid=35284066}}</ref>.<!-- The new version WHO indicates BCR::ABL1 is rare in AML, only accounts less than 0.5%, but the literature I found typically is 0.5-3%, the previous version also indicates the prevalence is <3%. Pls advice which number I should use. -->
+|Common (CML); Rare (AML).<!-- The new version WHO indicates BCR::ABL1 is rare in AML, only accounts less than 0.5%, but the literature I found typically is 0.5-3%, the previous version also indicates the prevalence is <3%. Pls advice which number I should use. -->
 |'''Diagnosis:''' BCR-ABL1 positive AML is an emerging entity. The proliferation of ''BCR-ABL1'' positive blasts present a diagnostic dilemma. While it may be difficult, it is essential to distinguish between BCR-ABL1 positive AML and Chronic Myeloid Leukemia in Myeloid Blast Crisis (CML-MBC), in order to choose the most appropriate therapy (e.g., intensive induction chemotherapy versus tyrosine kinase inhibitor (TKI) followed by an early allogeneic stem cell transplant). After the exclusion of acute leukemia of ambiguous lineage (a separate entity according to WHO) by flow cytometry, it is helpful to note any past history of antecedent hematological disease. Compared to CML-MBC, a higher percentage of blasts (median: 47% vs 13%), a lower percentage of basophils (median: 0% vs 2.5%) and absolute basophil count, a lower frequency of splenomegaly (25% vs 65%), lower cellularity, fewer dwarf megakaryocytes, and normal M:E ratio favor the diagnosis of BCR-ABL1 positive AML<ref name=":4" /><ref name=":3" />. The detection of p190 transcript and the occurrence of any BCR-ABL1 transcript in less than 100% of metaphases supports the diagnosis of AML rather than CML. Persistent CCyR (Complete Cytogenetic Response) after conventional chemotherapy is unusual for CML-MBC and supports the diagnosis of BCR-ABL1 positive AML<ref name=":2" />. Karyotype analysis that identifies the t(9;22)(q34;q11.2) translocation, either alone or in conjunction with additional chromosomal abnormalities, characterizes BCR-ABL1 positive AML<ref name=":3" /><ref name=":4" />. In addition, molecular methods including dual-colour dual-fusion FISH, RT-PCR, qPCR, and RNA or DNA sequencing are used to identify all common breakpoint variants when applicable.
@@ Line 86: / Line 86: @@
 BCR::ABL1 is generally favorable in CML<ref>{{Cite journal|last=Branford|first=Susan|last2=Yeung|first2=David T.|last3=Parker|first3=Wendy T.|last4=Roberts|first4=Nicola D.|last5=Purins|first5=Leanne|last6=Braley|first6=Jodi A.|last7=Altamura|first7=Haley K.|last8=Yeoman|first8=Alexandra L.|last9=Georgievski|first9=Jasmina|date=2014-07-24|title=Prognosis for patients with CML and >10% BCR-ABL1 after 3 months of imatinib depends on the rate of BCR-ABL1 decline|url=https://pubmed.ncbi.nlm.nih.gov/24859364|journal=Blood|volume=124|issue=4|pages=511–518|doi=10.1182/blood-2014-03-566323|issn=1528-0020|pmid=24859364}}</ref><ref>{{Cite journal|last=Lauseker|first=Michael|last2=Hehlmann|first2=Rüdiger|last3=Hochhaus|first3=Andreas|last4=Saußele|first4=Susanne|date=2023-11|title=Survival with chronic myeloid leukaemia after failing milestones|url=https://pubmed.ncbi.nlm.nih.gov/37726340|journal=Leukemia|volume=37|issue=11|pages=2231–2236|doi=10.1038/s41375-023-02028-2|issn=1476-5551|pmc=10624616|pmid=37726340}}</ref>.
-Three BCR-ABL chimeric proteins result from varying mRNA fusions of the ABL and BCR genes. The most common breakpoint occurs in BCR intron 13 or 14, fusing to ABL1 exon a2 (e13a2, e14a2), yielding a 210 kilodalton protein (p210 BCR-ABL1) found in 95% of CML cases. A rare alternative (<1%) is the e19a2 fusion, producing a 230 kilodalton protein (p230 BCR-ABL1), a marker for neutrophilic-chronic myeloid leukemia. The e1a2 fusion results in the p190 BCR-ABL1 protein, prevalent in B cell ALL, less common in AML, and rare in CML<ref name=":5" />.
+Three BCR-ABL chimeric proteins result from varying mRNA fusions of the ABL and BCR genes. The most common breakpoint occurs in BCR intron 13 or 14, fusing to ABL1 exon a2 (e13a2, e14a2), yielding a 210 kilodalton protein (p210 BCR-ABL1) found in 95% of CML cases. A rare alternative (<1%) is the e19a2 fusion, producing a 230 kilodalton protein (p230 BCR-ABL1), a marker for neutrophilic-chronic myeloid leukemia. The e1a2 fusion results in the p190 BCR-ABL1 protein, prevalent in B cell ALL, less common in AML, and rare in CML<ref name=":5">{{Cite journal|last=Al Hamad|first=Mohammad|date=2021|title=Contribution of BCR-ABL molecular variants and leukemic stem cells in response and resistance to tyrosine kinase inhibitors: a review|url=https://pubmed.ncbi.nlm.nih.gov/35284066|journal=F1000Research|volume=10|pages=1288|doi=10.12688/f1000research.74570.2|issn=2046-1402|pmc=8886173|pmid=35284066}}</ref>.