View source for HAEM5:B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features

{{DISPLAYTITLE:B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]

{{Under Construction}}

<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-11-03. The original page can be found at [[HAEM4:B-Lymphoblastic Leukemia/Lymphoma, BCR-ABL1-Like]].
}}</blockquote>
==Primary Author(s)*==
Mark G. Evans, MD, University of California, Irvine

Fabiola Quintero-Rivera, MD, University of California, Irvine

__TOC__

==Cancer Category/Type==
Acute Lymphoblastic Leukemia

==Cancer Sub-Classification / Subtype==
B-lymphoblastic leukemia/lymphoma, BCR-ABL1-like

==Definition / Description of Disease==
In 2009, a high-risk subgroup of B-ALL was identified in children, adolescents, and young adults<ref name=":0">{{Cite journal|last=Den Boer|first=Monique L.|last2=van Slegtenhorst|first2=Marjon|last3=De Menezes|first3=Renée X.|last4=Cheok|first4=Meyling H.|last5=Buijs-Gladdines|first5=Jessica G. C. A. M.|last6=Peters|first6=Susan T. C. J. M.|last7=Van Zutven|first7=Laura J. C. M.|last8=Beverloo|first8=H. Berna|last9=Van der Spek|first9=Peter J.|date=2009|title=A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study|url=https://www.ncbi.nlm.nih.gov/pubmed/19138562|journal=The Lancet. Oncology|volume=10|issue=2|pages=125–134|doi=10.1016/S1470-2045(08)70339-5|issn=1474-5488|pmc=2707020|pmid=19138562}}</ref><ref name=":1">{{Cite journal|last=Mullighan|first=Charles G.|last2=Su|first2=Xiaoping|last3=Zhang|first3=Jinghui|last4=Radtke|first4=Ina|last5=Phillips|first5=Letha A. A.|last6=Miller|first6=Christopher B.|last7=Ma|first7=Jing|last8=Liu|first8=Wei|last9=Cheng|first9=Cheng|date=2009|title=Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/19129520|journal=The New England Journal of Medicine|volume=360|issue=5|pages=470–480|doi=10.1056/NEJMoa0808253|issn=1533-4406|pmc=2674612|pmid=19129520}}</ref><ref>{{Cite journal|last=Roberts|first=Kathryn G.|last2=Morin|first2=Ryan D.|last3=Zhang|first3=Jinghui|last4=Hirst|first4=Martin|last5=Zhao|first5=Yongjun|last6=Su|first6=Xiaoping|last7=Chen|first7=Shann-Ching|last8=Payne-Turner|first8=Debbie|last9=Churchman|first9=Michelle L.|date=2012|title=Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/22897847|journal=Cancer Cell|volume=22|issue=2|pages=153–166|doi=10.1016/j.ccr.2012.06.005|issn=1878-3686|pmc=3422513|pmid=22897847}}</ref>. The genetic expression is similar to that of BCR-ABL1-positive cases, but without t(9;22)(q34.1;q11.2). Instead, BCR-ABL-1-like B-ALL is a genetically heterogenous disease, often with alterations activating cytokine receptors and tyrosine kinases. Several genetic expression profiles were initially utilized to recognize cases<ref name=":0" /><ref name=":1" />, however, different profiles did not always identify the same patients<ref name=":3">{{Cite journal|last=Boer|first=Judith M.|last2=Marchante|first2=João R. M.|last3=Evans|first3=William E.|last4=Horstmann|first4=Martin A.|last5=Escherich|first5=Gabriele|last6=Pieters|first6=Rob|last7=Den Boer|first7=Monique L.|date=2015|title=BCR-ABL1-like cases in pediatric acute lymphoblastic leukemia: a comparison between DCOG/Erasmus MC and COG/St. Jude signatures|url=https://www.ncbi.nlm.nih.gov/pubmed/26045294|journal=Haematologica|volume=100|issue=9|pages=e354–357|doi=10.3324/haematol.2015.124941|issn=1592-8721|pmc=4800707|pmid=26045294}}</ref>. Although emerging data advocates the therapeutic use of tyrosine kinase or JAK inhibitors in this disease process, BCR-ABL-like B-ALL is often associated with very high rates of relapse and poor overall survival; thus proper diagnosis is essential<ref>{{Cite journal|last=Roberts|first=Kathryn G.|last2=Reshmi|first2=Shalini C.|last3=Harvey|first3=Richard C.|last4=Chen|first4=I.-Ming|last5=Patel|first5=Kinnari|last6=Stonerock|first6=Eileen|last7=Jenkins|first7=Heather|last8=Dai|first8=Yunfeng|last9=Valentine|first9=Marc|date=2018|title=Genomic and outcome analyses of Ph-like ALL in NCI standard-risk patients: a report from the Children's Oncology Group|url=https://www.ncbi.nlm.nih.gov/pubmed/29997224|journal=Blood|volume=132|issue=8|pages=815–824|doi=10.1182/blood-2018-04-841676|issn=1528-0020|pmc=6107876|pmid=29997224}}</ref>.     

==Synonyms / Terminology==
Ph-like B-lymphoblastic leukemia/lymphoma

==Epidemiology / Prevalence==

*Ph-like ALL comprises up to 15% of childhood B-ALL, and 20 to 25% in adolescents and young adults<ref name=":4">{{Cite journal|last=Roberts|first=Kathryn G.|last2=Li|first2=Yongjin|last3=Payne-Turner|first3=Debbie|last4=Harvey|first4=Richard C.|last5=Yang|first5=Yung-Li|last6=Pei|first6=Deqing|last7=McCastlain|first7=Kelly|last8=Ding|first8=Li|last9=Lu|first9=Charles|date=2014|title=Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/25207766|journal=The New England Journal of Medicine|volume=371|issue=11|pages=1005–1015|doi=10.1056/NEJMoa1403088|issn=1533-4406|pmc=4191900|pmid=25207766}}</ref>.
*The incidence in adult patients is controversial—from 13-17% to up to 33% in some reports<ref>{{Cite journal|last=Boer|first=Judith M.|last2=Koenders|first2=Jasper E.|last3=van der Holt|first3=Bronno|last4=Exalto|first4=Carla|last5=Sanders|first5=Mathijs A.|last6=Cornelissen|first6=Jan J.|last7=Valk|first7=Peter J. M.|last8=den Boer|first8=Monique L.|last9=Rijneveld|first9=Anita W.|date=2015|title=Expression profiling of adult acute lymphoblastic leukemia identifies a BCR-ABL1-like subgroup characterized by high non-response and relapse rates|url=https://www.ncbi.nlm.nih.gov/pubmed/25769542|journal=Haematologica|volume=100|issue=7|pages=e261–264|doi=10.3324/haematol.2014.117424|issn=1592-8721|pmc=4486237|pmid=25769542}}</ref><ref name=":5">{{Cite journal|last=Herold|first=Tobias|last2=Schneider|first2=Stephanie|last3=Metzeler|first3=Klaus H.|last4=Neumann|first4=Martin|last5=Hartmann|first5=Luise|last6=Roberts|first6=Kathryn G.|last7=Konstandin|first7=Nikola P.|last8=Greif|first8=Philipp A.|last9=Bräundl|first9=Kathrin|date=2017|title=Adults with Philadelphia chromosome-like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis|url=https://www.ncbi.nlm.nih.gov/pubmed/27561722|journal=Haematologica|volume=102|issue=1|pages=130–138|doi=10.3324/haematol.2015.136366|issn=1592-8721|pmc=5210243|pmid=27561722}}</ref><ref name=":6">{{Cite journal|last=Jain|first=Nitin|last2=Roberts|first2=Kathryn G.|last3=Jabbour|first3=Elias|last4=Patel|first4=Keyur|last5=Eterovic|first5=Agda Karina|last6=Chen|first6=Ken|last7=Zweidler-McKay|first7=Patrick|last8=Lu|first8=Xinyan|last9=Fawcett|first9=Gloria|date=2017|title=Ph-like acute lymphoblastic leukemia: a high-risk subtype in adults|url=https://www.ncbi.nlm.nih.gov/pubmed/27919910|journal=Blood|volume=129|issue=5|pages=572–581|doi=10.1182/blood-2016-07-726588|issn=1528-0020|pmc=5290985|pmid=27919910}}</ref>.
*Higher rates of disease are observed in Hispanic and Native-American populations, and among children with Down syndrome<ref>{{Cite journal|last=Harvey|first=Richard C.|last2=Mullighan|first2=Charles G.|last3=Chen|first3=I.-Ming|last4=Wharton|first4=Walker|last5=Mikhail|first5=Fady M.|last6=Carroll|first6=Andrew J.|last7=Kang|first7=Huining|last8=Liu|first8=Wei|last9=Dobbin|first9=Kevin K.|date=2010|title=Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of IKZF1, Hispanic/Latino ethnicity, and a poor outcome in pediatric B-progenitor acute lymphoblastic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/20139093|journal=Blood|volume=115|issue=26|pages=5312–5321|doi=10.1182/blood-2009-09-245944|issn=1528-0020|pmc=2902132|pmid=20139093}}</ref>.

==Clinical Features==

Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
{| class="wikitable"
|'''Signs and Symptoms'''
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)

EXAMPLE B-symptoms (weight loss, fever, night sweats)

EXAMPLE Fatigue

EXAMPLE Lymphadenopathy (uncommon)
|-
|'''Laboratory Findings'''
|EXAMPLE Cytopenias

EXAMPLE Lymphocytosis (low level)
|}


<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
The presenting symptoms are similar to those of other ALL patients, with the exception of potentially higher white blood cell counts<ref name=":2">Borowitz MJ, et al., (2017). B-lymphoblastic leukaemia/lymphoma with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p208.</ref>.

</blockquote>
==Sites of Involvement==
Bone marrow

==Morphologic Features==
There are no morphological or cytochemical features that aid in the diagnosis. Blasts range from small to large and chromatin varying from immature to more mature, corresponding to French-American-British classification L1 or L2 subtype<ref name=":7">{{Cite journal|last=Konoplev|first=Sergej|last2=Lu|first2=Xinyan|last3=Konopleva|first3=Marina|last4=Jain|first4=Nitin|last5=Ouyang|first5=Juan|last6=Goswami|first6=Maitrayee|last7=Roberts|first7=Kathryn G.|last8=Valentine|first8=Marc|last9=Mullighan|first9=Charles G.|date=2017|title=CRLF2-Positive B-Cell Acute Lymphoblastic Leukemia in Adult Patients: A Single-Institution Experience|url=https://www.ncbi.nlm.nih.gov/pubmed/28340183|journal=American Journal of Clinical Pathology|volume=147|issue=4|pages=357–363|doi=10.1093/ajcp/aqx005|issn=1943-7722|pmid=28340183}}</ref>.[[File:Morphologic Features.jpg|thumb|195x195px|(Konoplev et al. Am J Clin Pathol. 2017.)|link=http://www.ccga.io/index.php/File:Morphologic_Features.jpg|none]]

==Immunophenotype==

Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>

{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||EXAMPLE CD1
|-
|Positive (subset)||EXAMPLE CD2
|-
|Negative (universal)||EXAMPLE CD3
|-
|Negative (subset)||EXAMPLE CD4
|}


<blockquote class='blockedit'>{{Box-round|title=v4:Immunophenotype|The content below was from the old template. Please incorporate above.}}
Blasts are typically CD19, TdT, and CD10-positive. By flow cytometry, a subset of cases with CRLF2 translocations show very high levels of surface protein expression<ref name=":2" />.

</blockquote>
==Chromosomal Rearrangements (Gene Fusions)==

Put your text here and fill in the table

{| class="wikitable sortable"
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
EXAMPLE 30% (add reference)
|Yes
|No
|Yes
|EXAMPLE

The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
|}		
			

<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}
Tyrosine kinase-type translocations are common and involve ''ABL1'' and other kinases (such as ''ABL2'', ''EPOR'', ''JAK2'', ''PDGFRB'', and ''CSF1R''); more than 30 gene partners have been described. Frequently reported examples include ''IGH''–''EPOR'' of the t(14;19)(q32;p13)/ins(14;19)(q32;p13), ''EBF1''–''PDGFRB'' of the del(5)(q32q33.3), ''NUP214''–''ABL1'' of the t(9;9)(q34;q34)/del(9)(q34q34), and ''ETV6''–''ABL1'' of the t(9;12)(q34;p13). Other notable fusions are ''BCR''–''JAK2'', ''PAX5''–''JAK2'', ''STRN3''–''JAK2'', ''RANBP2''–''ABL1'', ''RCSD1''–''ABL1'', and ''MEF2D''–''CSF1R''<ref>Heim S & Mitelman F. Cancer Cytogenetics: Chromosomal and Molecular Genetic Aberrations of Tumor Cells. John Wiley & Sons, Incorporated: Chichester, United Kingdom. 2015.</ref>.

</blockquote>


<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
* Chromosomal Rearrangements (Gene Fusions)
* Individual Region Genomic Gain/Loss/LOH
* Characteristic Chromosomal Patterns
* Gene Mutations (SNV/INDEL)}}

*Diagnosis:  Definitive diagnosis is based on two major gene expression signatures (DCOG/Erasmus MC and COG/St. Jude).
**DCOG/Erasmus MC incorporates hierarchal clustering of microarrays using a 110-gene probe set; this genetic signature frequently detected deletions in ''IKZF1'', dic(9;20), and iAMP21 in BCR-ABL1-like B-ALL<ref name=":0" />.
**COG/St. Jude employs predictive analysis of microarrays using a 257-gene probe set; this genetic signature demonstrated primarily activating kinase or cytokine receptor signaling alterations, in addition to ''IKZF1'' deletions<ref name=":1" />.
*Prognosis:  In both pediatric and adult populations, BCR-ABL1-like B-ALL is associated with high rates of relapse and poor prognosis.
**The median 5-year overall survival rates for children with BCR-ABL1-like B-ALL, adolescents, and young adults was 72.8%, 65.8%, and 25.8%, respectively<ref name=":4" />.
**Median 5-year-overall survival in adults was 22%, versus 64% in comparable patients with non-BCR-ABL1, non-BCR-ABL1-like, and non-MLL translocation B-ALL<ref name=":5" />.
*Therapeutic Implications:  Due to the aggressive nature of the disease, patients are often treated with high-intensity chemotherapy regimens, such as hyper-CVAD or an augmented Berlin-Frankfurt-Münster regimen<ref name=":6" />.
**However, given the high incidence of fusions involving ''JAK2'', ''ABL1'', ''ABL2'', and other tyrosine kinases, tyrosine kinase inhibitors and JAK inhibitors are now being trialed clinically<ref name=":4" /><ref>{{Cite journal|last=Tasian|first=Sarah K.|last2=Doral|first2=Michelle Y.|last3=Borowitz|first3=Michael J.|last4=Wood|first4=Brent L.|last5=Chen|first5=I.-Ming|last6=Harvey|first6=Richard C.|last7=Gastier-Foster|first7=Julie M.|last8=Willman|first8=Cheryl L.|last9=Hunger|first9=Stephen P.|date=2012|title=Aberrant STAT5 and PI3K/mTOR pathway signaling occurs in human CRLF2-rearranged B-precursor acute lymphoblastic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/22685175|journal=Blood|volume=120|issue=4|pages=833–842|doi=10.1182/blood-2011-12-389932|issn=1528-0020|pmc=3412346|pmid=22685175}}</ref><ref>{{Cite journal|last=Iacobucci|first=Ilaria|last2=Li|first2=Yongjin|last3=Roberts|first3=Kathryn G.|last4=Dobson|first4=Stephanie M.|last5=Kim|first5=Jaeseung C.|last6=Payne-Turner|first6=Debbie|last7=Harvey|first7=Richard C.|last8=Valentine|first8=Marcus|last9=McCastlain|first9=Kelly|date=2016|title=Truncating Erythropoietin Receptor Rearrangements in Acute Lymphoblastic Leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/26859458|journal=Cancer Cell|volume=29|issue=2|pages=186–200|doi=10.1016/j.ccell.2015.12.013|issn=1878-3686|pmc=4750652|pmid=26859458}}</ref>.

</blockquote>
==Individual Region Genomic Gain/Loss/LOH==

Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span>

{| class="wikitable sortable"
|-
!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE

7
|EXAMPLE Loss
|EXAMPLE

chr7:1- 159,335,973 [hg38]
|EXAMPLE

chr7
|Yes
|Yes
|No
|EXAMPLE

Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
|-
|EXAMPLE

8
|EXAMPLE Gain
|EXAMPLE

chr8:1-145,138,636 [hg38]
|EXAMPLE

chr8
|No
|No
|No
|EXAMPLE

Common recurrent secondary finding for t(8;21) (add reference).
|}

<blockquote class='blockedit'>{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}
Monoallelic (often partial) deletion of the IKAROS transcription factor, encoded by ''IKZF1'', is one of the most frequently observed genetic abnormalities in BCR-ABL1-like B-ALL, although this finding is not specific and not included in the definition<ref name=":3" />. 
</blockquote>
==Characteristic Chromosomal Patterns==

Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis'')</span>

{| class="wikitable sortable"
|-
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE

Co-deletion of 1p and 18q
|Yes
|No
|No
|EXAMPLE:

See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|}

<blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}
Approximately half of cases demonstrate rearrangements resulting in overexpression of CRLF2<ref name=":7" />. These rearrangements are the result of either translocation of immunoglobin heavy chain enhance locus into ''CRLF2'' (''IGH''-''CRLF2''—more commonly seen in adults) or through a cryptic deletion on chromosome X/Y involving the PAR1 psuedoautosomal region, resulting in fusion of ''CRLF2'' to ''P2RY8'' (more commonly seen in children). Very rare alternative translocations involving ''CRLF2'' have also been observed.
[[File:FISH 1.jpg|thumb|none]]

[[File:FISH 2.jpg|thumb|none]]

[Abnormal FISH results in interphase nuclei from a bone marrow sample using the ''CRLF2'' dual-color, break-apart (Cytocell) and ''IGH'' dual-color, break-apart probes, reflective of ''IGH''-''CRLF2'' fusion]
[[File:FISH 3.jpg|thumb|none]]

[[File:Karyotype.jpg|thumb|none]]

[Concurrent abnormal karyotype with trisomy 21 and a translocation involving chromosomes X, 14, and 2 in 9 of 13 cells available for analysis. Metaphase FISH with the ''IGH'' break-apart probe (Vysis) confirms the presence of 5’ ''IGH'' (green signal) on the abnormal chromosome Xp33.1 (''CRLF2'' locus), highly suggestive on an ''IGH''-''CRLF2'' fusion rearrangement.

47,XX,+21c[4]/47,idem,der(X)t(X;14)(p33.1;q32),der(2)t(2;14)(p11.2;q11.2)t(X;14),der(14)t(2;14)[5]/46,XX[4].ish der(X)(5’IGH+),der(2)(3’IGH+)]

(Images courtesy of Fabiola Quintero-Rivera, MD)

</blockquote>
==Gene Mutations (SNV/INDEL)==

Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity.'') </span>

{| class="wikitable sortable"
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
!'''Diagnostic Significance (Yes, No or Unknown)'''
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE: TP53; Variable LOF mutations

EXAMPLE:

EGFR; Exon 20 mutations

EXAMPLE: BRAF; Activating mutations
|EXAMPLE: TSG
|EXAMPLE: 20% (COSMIC)

EXAMPLE: 30% (add Reference)
|EXAMPLE: IDH1 R123H
|EXAMPLE: EGFR amplification
|
|
|
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
<br />
|}
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.


<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}
In addition to gene translocations, gain-of-function mutations in ''CRLF2'' itself or in its partner gene, ''IL7RA'', have been seen<ref name=":8">Quesada A, Reynolds M, Jorgensen JL, et al. Cytokine receptor-like factor 2 (CRLF2) expression in precursor B-lymphoblastic leukemia. International Clinical Cytometry Society e-Newsletter. 2014;5(1).</ref>.  Alternative alterations activating kinase signaling occur, including activating mutations of ''FLT3'', as well as focal deletions of ''SH2B3'' (also known as ''LNK'')<ref>Tosi S & Reid AG. The Genetic Basis of Haematological Cancers. John Wiley & Sons, Incorporated: Chichester, United Kingdom: 2016.</ref>.

Herold et al. in 2017 reported a wide variety of molecular alterations in BCR-ABL1-like B-ALL, which was shown to have statistically significant associations with alterations of ''IKZF1'', ''CRLF2'', ''JAK2'', ''BTG1'', and high ''CRLF2'' expression<ref name=":5" />.

</blockquote>
==Epigenomic Alterations==
Not applicable

==Genes and Main Pathways Involved==

Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>
{| class="wikitable sortable"
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|EXAMPLE: BRAF and MAP2K1; Activating mutations
|EXAMPLE: MAPK signaling
|EXAMPLE: Increased cell growth and proliferation
|-
|EXAMPLE: CDKN2A; Inactivating mutations
|EXAMPLE: Cell cycle regulation
|EXAMPLE: Unregulated cell division
|-
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
|EXAMPLE:  Histone modification, chromatin remodeling
|EXAMPLE:  Abnormal gene expression program
|}

<blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}

*IKAROS transcription factor:  Deletion of ''IKZF1'' results in activation of ''EBF1'', ''MSH2'', and ''MCL1'', leading to B-cell leukemogenesis<ref>{{Cite journal|last=van der Veer|first=Arian|last2=Waanders|first2=Esmé|last3=Pieters|first3=Rob|last4=Willemse|first4=Marieke E.|last5=Van Reijmersdal|first5=Simon V.|last6=Russell|first6=Lisa J.|last7=Harrison|first7=Christine J.|last8=Evans|first8=William E.|last9=van der Velden|first9=Vincent H. J.|date=2013|title=Independent prognostic value of BCR-ABL1-like signature and IKZF1 deletion, but not high CRLF2 expression, in children with B-cell precursor ALL|url=https://www.ncbi.nlm.nih.gov/pubmed/23974192|journal=Blood|volume=122|issue=15|pages=2622–2629|doi=10.1182/blood-2012-10-462358|issn=1528-0020|pmc=3795461|pmid=23974192}}</ref>.
*''CRLF2'' overexpression:  CRFL2 and its cofactor IL7RA form a receptor for thymic stromal-derived lymphopoietin that activates the JAK2-signal transducer and upregulates the transcription 5 pathway<ref name=":8" />.
*Dysregulation of several tyrosine kinase signaling pathways (involving ''ABL1'', ''ABL2'', ''PDGFRB'', ''CSF1'', etc.) results in B-cell progenitor proliferation.

</blockquote>
==Genetic Diagnostic Testing Methods==

*Flow cytometry for ''CRLF2'' has been shown in some studies to be 100% concordant with FISH results<ref name=":7" />.
*Next-generation sequencing is helpful for detecting copy number changes, single nucleotide variants, and gene fusions involving ''CRLF2'', ''ABL1'', ''ABL2'', ''JAK2'', etc.
*Gene expression profile algorithms, incorporating prediction analysis or hierarchical clustering of microarrays, provide the definitive diagnosis of BCR-ABL1-like B-ALL.

==Familial Forms==
Families with certain inherited variants of ''GATA3'' (often seen in Native-American populations) are at increased risk of BCR-ABL1-like B-ALL<ref>{{Cite journal|last=Perez-Andreu|first=Virginia|last2=Roberts|first2=Kathryn G.|last3=Harvey|first3=Richard C.|last4=Yang|first4=Wenjian|last5=Cheng|first5=Cheng|last6=Pei|first6=Deqing|last7=Xu|first7=Heng|last8=Gastier-Foster|first8=Julie|last9=E|first9=Shuyu|date=2013|title=Inherited GATA3 variants are associated with Ph-like childhood acute lymphoblastic leukemia and risk of relapse|url=https://www.ncbi.nlm.nih.gov/pubmed/24141364|journal=Nature Genetics|volume=45|issue=12|pages=1494–1498|doi=10.1038/ng.2803|issn=1546-1718|pmc=4039076|pmid=24141364}}</ref>. 

==Additional Information==

Put your text here

==Links==
[[CRLF2]] 

[[ABL1]] 

[[ABL2]] 

[[JAK2]] 

[[PDGFRB]] 

[[IKZF1]] 

Pre-B ALL B-lymphoblastic leukemia/lymphoma with ''BCR-ABL1''-like/Ph-like in Pathology Outlines (http://www.pathologyoutlines.com/topic/leukemiaprebbcrabl1like.html) 

==References==
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==Notes==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
<nowiki>*</nowiki>''Citation of this Page'': “B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:B-lymphoblastic_leukaemia/lymphoma_with_BCR::ABL1-like_features</nowiki>.
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases B]]