Acute undifferentiated leukemia (AUL) is a form of acute leukemia of ambiguous lineage (ALAL). In these types of leukemia, there is no distinct cell lineage, either lymphoid or myeloid, with some cells expressing characteristics of more than one cell type. In AUL, the cancer cells cannot be assigned to a specific lineage. Genetic correlation has yet to be ascertained. Due to the rarity of the disease, its natural history and prevalence are not known [1] [2]. Furthermore, AUL and other ALALs have no distinct features, and so cannot be distinguished clinically.

AUL is thought to originate from immature or poorly differentiated hematopoietic stem cells. These blast cells cannot be classified as they do not display lineage specific markers. AUL is seen in various age groups, but is most frequent after the 6th decade. Leukemias that present during this time period are associated with a poor prognosis, with a five year survival rate as low as 3% [3].

AUL presents similarly to other acute leukemias, typically with anemia and several bleeding diatheses. Bleeding may be from the skin, gastrointestinal tract and reproductive system, evidenced by epistaxis, petechiae, ecchymosis, hematuria, and abnormal uterine bleeding. Additional symptoms such as weight loss, malaise, fever and fatigue may be experienced. Individuals may also present with infections, which can be severe. They are more susceptible to infection due to the reduced production of normal white blood cells.

Other possible manifestations are bone pain (from bone involvement), meningitis, lymphadenopathy, hepatomegaly, splenomegaly, and cutaneous lesions (leukemia cutis).

• Cervical Lymphadenopathy

  In addition, the patient had bilateral cervical lymphadenopathy, bilateral tonsillar enlargement and hepatosplenomegaly. [omicsonline.org]

• Easy Bruising

  Acute leukemia of unspecified cell type Corresponding ICD-10 Codes C95.0 Acute leukemia of unspecified cell type Corresponding ICD-10-CM Codes (U.S. only) C95.0 Acute leukemia of unspecified cell type (effective October 01, 2015) Signs and Symptoms Easy [seer.cancer.gov]

  A lack of platelets can lead to easy bruising or bleeding with minor trauma. The early signs of AML are often vague and nonspecific, and may be similar to those of influenza or other common illnesses. [en.wikipedia.org]

• Anemia

  The mRNA encoding the major bcr/abl fusion protein then appeared in the stage of sideroblastic anemia. Finally, the mRNA encoding both major and minor bcr/abl was detected in the stage of AUL transformation. [ncbi.nlm.nih.gov]

  […] de 69 años, conocido hipertenso, ex tabaquista y ex etilista, el cual consulta al Primer Nivel con historia de 2 meses de evolución de tos no productiva, adinamia, prurito generalizado, hiporexia y pérdida de peso de 4 kilogramos; el hemograma mostró anemia [go.gale.com]

  The patients present with leukocytosis, anemia, variable platelet count and a variety of nonspecific symptoms related to ineffective hematopoesis (fatigue, bleeding and bruising, recurrent infections, bone pain) and/or extramedullary site involvement [orpha.net]

  AUL presents similarly to other acute leukemias, typically with anemia and several bleeding diatheses. [symptoma.com]

• Pallor

  The physical examination revealed mild pallor, purpuric spots over trunk and thighs. In addition, the patient had bilateral cervical lymphadenopathy, bilateral tonsillar enlargement and hepatosplenomegaly. [omicsonline.org]

  Pallor may be obvious. Signs of infection can be nonspecific. Fever or pneumonia may present. Thrombocytopenia often causes petechiae on the lower limbs. DIC may aggravate the situation and cause larger lesions. [patient.info]

• Productive Cough

  We present the case of a 69 years male, hypertensive, former smoker and drinker, who consults to the first level of attention with a 2 months history of not productive cough, asthenia, itching, hiporexia and a loss of weight of 4 kilograms, the hemogram [go.gale.com]

• Petechiae

  Bleeding may be from the skin, gastrointestinal tract and reproductive system, evidenced by epistaxis, petechiae, ecchymosis, hematuria, and abnormal uterine bleeding. [symptoma.com]

  Corresponding ICD-10-CM Codes (U.S. only) C95.0 Acute leukemia of unspecified cell type (effective October 01, 2015) Signs and Symptoms Easy bruising or bleeding Eczema-like skin rash Fatigue Fever Night sweats Pain or feeling of fullness below the rib s Petechiae [seer.cancer.gov]

  Thrombocytopenia often causes petechiae on the lower limbs. DIC may aggravate the situation and cause larger lesions. Petechiae are small dots, purpura is larger and ecchymoses are larger bruises. Hepatomegaly and splenomegaly may be found. [patient.info]

  Some generalized symptoms include fever, fatigue, weight loss or loss of appetite, shortness of breath, anemia, easy bruising or bleeding, petechiae (flat, pin-head sized spots under the skin caused by bleeding), bone and joint pain, and persistent or [en.wikipedia.org]

The diagnosis of acute undifferentiated leukemia is one of exclusion. Although AUL cannot be clinically differentiated from other types of acute leukemia, there are several techniques that are available for diagnosis. These include:

• Immunohistochemistry [4] [5]
• Cytochemistry [6]
• Flow cytometric immunophenotyping
• Microscopy

These tests are used to identify lineage-specific markers, which are lacking in AUL. Leukemic blast cells in AUL express markers that are non-specific. Often, AULs express cluster of differentiation (CD) markers CD7, CD13, and human leukocyte antigen-D related (HLA-DR) [1] [2].

Investigations carried out for acute leukemia include:

• Full blood count: This will show pancytopenia in the case of an acute leukemia. The presence of large numbers of blast cells is also indicative of acute leukemia.
• Comprehensive metabolic panel: This may reveal electrolyte derangements and other abnormal parameters, such as hyperuricemia, hypocalcemia, hyper- or hypokalemia, hypoglycemia, high levels of lactate dehydrogenase and elevated liver enzymes.
• Peripheral smear.
• Bone marrow biopsy or aspirate.
• Imaging: Computerized tomography (CT), magnetic resonance imaging (MRI), ultrasound and X-rays are sometimes used to test for central nervous system, chest or abdominal spread of the leukemia.

However, the fact that it is an undifferentiated leukemia may affect the decisions regarding further treatment after the initial treatment. [oncolink.org]

These results may be direct evidence for the induction of the bcr/abl fusion gene by treatment with an alkylating agent (ifosphamide). [ncbi.nlm.nih.gov]

This issue of Emerging Cancer Therapeutics provides a comprehensive review for practitioners on the current status of leukemia treatment. [books.google.de]

Conn's Current Therapy 2004, 56th ed., Copyright © 2004 Elsevier Ferri: Ferri's Clinical Advisor: Instant Diagnosis and Treatment, 2004 ed., Copyright © 2004 Mosby, Inc [nethealthbook.com]

Clinical features, clonal karyotypes, and response to treatment were also examined. [ohsu.pure.elsevier.com]

Clinically, these diagnostic features matched with a poor prognosis, being associated with refractoriness to treatment, relapse and progression of disease, antecedent hematologic abnormality, and other malignancy. [ncbi.nlm.nih.gov]

This acute leukemia carries a poor prognosis. [path.upmc.edu]

These data suggest that the majority of cases of AUL can be reclassified as either myeloid or lymphoid leukemias, that AUL is associated with a high frequency of chromosomal abnormalities, and that AUL carries a very poor prognosis. [ohsu.pure.elsevier.com]

As Virchow was uncertain of the etiology of the white blood cell excess, he used the purely descriptive term "leukemia" (Greek: "white blood") to refer to the condition. [98] Further advances in the understanding of acute myeloid leukemia occurred rapidly [en.wikipedia.org]

Eczema-like skin rash Fatigue Fever Night sweats Pain or feeling of fullness below the rib s Petechiae Shortness of breath Weakness Diagnostic Exams Immunophenotyping Lumbar puncture Molecular testing Peripheral blood smear Progression and Transformation None Epidemiology [seer.cancer.gov]

Epidemiology These rare leukemias account for less than 4% of all cases of acute leukemia and occur in all age groups but are more frequent in adults. [wiki.clinicalflow.com]

BCR-ABL1 Mixed phenotype acute leukemia with t(v;11q23); MLL rearranged Mixed phenotype acute leukemia, B/myeloid, NOS Mixed phenotype acute leukemia, T/myeloid, NOS Mixed phenotype acute leukemia, NOS rare types Other acute leukemias of ambiguous lineage Epidemiology [pathologyoutlines.com]

See also the following: Epidemiology Acute undifferentiated leukemia (AUL) is extremely rare, and little is known about the frequency of this disease. [emedicine.medscape.com]

In rare cases, people with AML can develop a chloroma, or solid tumor of leukemic cells outside the bone marrow, which can cause various symptoms depending on its location. [7] An important pathophysiological mechanism of leukemogenesis in AML is the [en.wikipedia.org]

Collaborative overview of randomised trials of antiplatelet therapy, I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. ‎ [books.google.de]

NCT01137643 Recruiting 18 - 120 Years old NO Healthy Volunteers NO Placebo Refractory Acute Myeloid Leukemia Clinical Trial This phase II trial studies how well selective T cell depletion works in preventing graft-versus-host disease (GVHD) in patients [patientwing.com]

They now understand that in normal conditions, SET "masks" histones by wrapping itself around the ends of the protein chains, helping to prevent random commands from using the histones on the DNA to activate genes inappropriately – and therefore protecting [sciencedaily.com]

This mutated cell, called a blast because it is not a fully grown cell (thus the word "Blastic" in Blastic Plasmacytoid Dendritic Cell Neoplasm), then proliferates through the bone marrow and blood stream, preventing normal development of other cells [yippee-leukemia.blogspot.com]

[…] doxorubin, melphalan, and mitoxantrone Exposure to high doses of radiation Certain blood disorders such as myeloproliferative disorders (for example, chronic myelogenous leukemia) A parent, brother, or sister who has had AML Although there is no way to prevent [webmd.com]

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2. Bassan R, Biondi A, Benvestito S, et al. Acute undifferentiated leukemia with CD7+ and CD13+ immunophenotype. Lack of molecular lineage commitment and association with poor prognostic features. Cancer. 1992;69(2):396-404.
3. Dores GM, Devesa SS, Curtis RE, Linet MS, Morton LM. Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007. Blood. 2012;119(1):34-43.
4. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-2405.
5. Arber DA, Borowitz MJ, Cessna M, et al. Initial diagnostic workup of acute leukemia: guideline from the College of American Pathologists and the American Society of Hematology. Arch Pathol Lab Med. 2017 Feb 22.
6. Porwit A, Béné MC. Acute leukemias of ambiguous origin. Am J Clin Pathol. 2015;144(3):361-376.