Bailey.Glen at 21:30, 4 December 2023

2023-12-04T21:30:13Z

← Older revision		Revision as of 16:30, 4 December 2023
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	-CD7 positivity is associated with T cells, but can also be seen in some CD34+ hematopoietic stem cells and is not unexpected in a stem cell leukemia<ref name=":0" />.		-CD7 positivity is associated with T cells, but can also be seen in some CD34+ hematopoietic stem cells and is not unexpected in a stem cell leukemia<ref name=":0" />.

	-See [[Acute Leukemias of Ambiguous Lineage]] for assigning lineage assignment.		-See [[HAEM4:Acute Leukemias of Ambiguous Lineage]] for assigning lineage assignment.

	==Chromosomal Rearrangements (Gene Fusions)==		==Chromosomal Rearrangements (Gene Fusions)==
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	==Links==		==Links==

	[[Acute Leukemias of Ambiguous Lineage]]		[[HAEM4:Acute Leukemias of Ambiguous Lineage]]

	[[Mixed ~~Phenotype Acute Leukemia (MPAL)~~, B/~~Myeloid, Not Otherwise Specified~~]]		[[HAEM5:Mixed-phenotype acute leukaemia, B/myeloid]]

	==References==		==References==

Bailey.Glen at 18:47, 3 November 2023

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 ==Primary Author(s)*==
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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.

Bailey.Glen: Created page with "==Primary Author(s)*== Amelia Nakanishi, MD and Shashi Shetty, PhD TOC ==Cancer Category/Type== Hematologic malignancy/ Acute leukemia ==Cancer Sub-Classification /..."

2023-11-03T18:08:19Z

Created page with "==Primary Author(s)*== Amelia Nakanishi, MD and Shashi Shetty, PhD __TOC__ ==Cancer Category/Type== Hematologic malignancy/ Acute leukemia ==Cancer Sub-Classification /..."

New page

==Primary Author(s)*==

Amelia Nakanishi, MD and Shashi Shetty, PhD

__TOC__

==Cancer Category/Type==

Hematologic malignancy/ Acute leukemia

==Cancer Sub-Classification / Subtype==

Acute Leukemias of Ambiguous Lineage (WHO 2017)/ Acute Undifferentiated Leukemia (AUL)

==Definition / Description of Disease==

An acute leukemia with blasts that are immunophenotypically ambiguous for any one hematopoietic lineage. AUL is a diagnosis of exclusion that is incompatible with the presence of features that meet the criteria for inclusion in any of the other AML groups (i.e. AML with Recurrent Genetic Abnormalities, AML with Myelodysplasia-Related Changes, or Therapy-Related Myeloid Neoplasms).

To support an undifferentiated phenotype, AUL requires an immunophenotypic work up that “excludes unusual lineages such as plasmacytoid dendritic cell precursors, natural killer precursors, basophils, and non-hematologic cells”<ref name=":0">Borowitz MJ, et al., (2017). Acute leukaemias of ambiguous lineage, 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, p182.</ref>.

==Synonyms / Terminology==

Blast cell leukemia, stem cell leukemia, stem cell acute leukemia, undifferentiated leukemia.

==Epidemiology / Prevalence==

Very rare; precise frequency unknown.

==Clinical Features==

In one study of 16 cases of adults with AUL, the median age was 63 years (range: 24-84 years) and patients could achieve clinical remission after allogeneic stem cell transplantation<ref name=":2">{{Cite journal|displayauthors=1|last=Heesch|first=Sandra|last2=Neumann|first2=Martin|last3=Schwartz|first3=Stefan|last4=Bartram|first4=Isabelle|last5=Schlee|first5=Cornelia|last6=Burmeister|first6=Thomas|last7=Hänel|first7=Matthias|last8=Ganser|first8=Arnold|last9=Heuser|first9=Michael|date=2013|title=Acute leukemias of ambiguous lineage in adults: molecular and clinical characterization|url=https://pubmed.ncbi.nlm.nih.gov/23412561|journal=Annals of Hematology|volume=92|issue=6|pages=747–758|doi=10.1007/s00277-013-1694-4|issn=1432-0584|pmid=23412561|via=}}</ref>. In previous studies that weakly suggest ALL induction regimens over AML induction regimens, there may be selection bias in the patients who were well enough to be transplant candidates<ref>{{Cite journal|displayauthors=1|last=Weinberg|first=Olga K.|last2=Hasserjian|first2=Robert P.|last3=Baraban|first3=Ezra|last4=Ok|first4=Chi Young|last5=Geyer|first5=Julia T.|last6=Philip|first6=John K. S. S.|last7=Kurzer|first7=Jason H.|last8=Rogers|first8=Heesun J.|last9=Nardi|first9=Valentina|date=2019|title=Clinical, immunophenotypic, and genomic findings of acute undifferentiated leukemia and comparison to acute myeloid leukemia with minimal differentiation: a study from the bone marrow pathology group|url=https://pubmed.ncbi.nlm.nih.gov/31000771|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=32|issue=9|pages=1373–1385|doi=10.1038/s41379-019-0263-3|issn=1530-0285|pmid=31000771|via=}}</ref>.

In children, based on limited clinical information in the literature, AUL has been associated with a poor prognosis<ref>{{Cite journal|displayauthors=1|last=Lee|first=Hyun Gyung|last2=Baek|first2=Hee Jo|last3=Kim|first3=Ho Sung|last4=Park|first4=Soo Min|last5=Hwang|first5=Tai Ju|last6=Kook|first6=Hoon|date=2019|title=Biphenotypic acute leukemia or acute leukemia of ambiguous lineage in childhood: clinical characteristics and outcome|url=https://pubmed.ncbi.nlm.nih.gov/30956966|journal=Blood Research|volume=54|issue=1|pages=63–73|doi=10.5045/br.2019.54.1.63|issn=2287-979X|pmc=6439300|pmid=30956966|via=}}</ref>.

==Sites of Involvement==

Bone marrow and peripheral blood. AUL is so rare, it is unknown if there is a pattern of other sites of involvement.

==Morphologic Features==

AUL blast morphology is bland and non-specific. Cytoplasmic granulation and disease defining morphology are absent.

==Immunophenotype==

Per WHO 2017, AUL blasts should express no more than one membrane marker for any lineage.

{| class="wikitable sortable"
|-
|Positive (universal)||Precursor stage''':''' HLA-DR, CD34, and/or CD38, CD117, CD133 <ref>Hoffman R, et al., (2018) Hematology, basic principles and practice, 7th edition. Elsevier: Philadelphia. (clinical key excerpt)</ref>
|-
|Positive (subset)||TdT
CD7 (weak positivity) see below.
|-
|Negative (universal)||Myeloid: MPO
Monocytic: NSE, CD11c, Cd14, CD64, lysozyme, Cd4, CD11b, CD36, NG2 homologue

T cell: cCD3

B cell: cCD22, cCD79a, strong CD19

Megakaryocytic: CD41, CD61, CD42, CD235a
|-
|Negative (subset)||NA
|}
Additional Description: Blasts are generally positive for HLA-DR, CD34, and/or CD38.

-CD7 positivity is associated with T cells, but can also be seen in some CD34+ hematopoietic stem cells and is not unexpected in a stem cell leukemia<ref name=":0" />.

-See [[Acute Leukemias of Ambiguous Lineage]] for assigning lineage assignment.

==Chromosomal Rearrangements (Gene Fusions)==

NA
==Characteristic Chromosomal Aberrations / Patterns==

AUL is associated with a high rate of chromosomal abnormalities, but have no characteristic abnormalities<ref name=":2" />.

==Genomic Gain/Loss/LOH==

NA
==Gene Mutations (SNV/INDEL)==

PHF6 a tumor suppressor gene may have implications in AUL though the evidence is limited.
===Other Mutations===
NA

==Epigenomics (Methylation)==

Unknown

==Genes and Main Pathways Involved==

Overexpression of BAALC, ERG, and MN1<ref name=":0" />.

==Diagnostic Testing Methods==

Morphology, immunohistochemistry, cytochemistry, flow cytometry, cytogenetics, and next generation sequencing.

==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==

There is evidence that the genes associated with poor prognosis in acute leukemias, BAALC, ERG, and MN1, are also overexpressed in AUL<ref name=":0" />.

==Familial Forms==

Unknown

==Other Information==

Although AUL and AML with minimal differentiation are both rare diagnoses, they have similar patient demographics and clinical courses. AUL and AML with minimal differentiation have different molecular abnormalities<ref name=":2" />.

==Links==

[[Acute Leukemias of Ambiguous Lineage]]

[[Mixed Phenotype Acute Leukemia (MPAL), B/Myeloid, Not Otherwise Specified]]

==References==

<references />
==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.

HAEM4:Acute Undifferentiated Leukemia - Revision history

Bailey.Glen at 21:30, 4 December 2023

Bailey.Glen at 18:47, 3 November 2023

Bailey.Glen: Created page with "==Primary Author(s)*== Amelia Nakanishi, MD and Shashi Shetty, PhD __TOC__ ==Cancer Category/Type== Hematologic malignancy/ Acute leukemia ==Cancer Sub-Classification /..."

Bailey.Glen: Created page with "==Primary Author(s)*== Amelia Nakanishi, MD and Shashi Shetty, PhD TOC ==Cancer Category/Type== Hematologic malignancy/ Acute leukemia ==Cancer Sub-Classification /..."