Cancer Report

Cancer : Acute lymphocytic leukemia
Summary
Cancer Name Acute lymphocytic leukemia
Cancer Alias ALL
Description "Adult acute lymphoblastic leukemia (ALL; also called acute lymphocytic leukemia) is a cancer of the blood and bone marrow. This type of cancer usually gets worse quickly if it is not treated.
Childhood acute lymphoblastic leukemia (also called acute lymphocytic leukemia or ALL) is a cancer of the blood and bone marrow. This type of cancer usually gets worse quickly if it is not treated. It is the most common type of cancer in children.
Normally, the bone marrow makes stem cells (immature cells) that develop into mature blood cells. There are 3 types of mature blood cells:
  • Red blood cells that carry oxygen and other materials to all tissues of the body.
  • White blood cells that fight infection and disease.
  • Platelets that help prevent bleeding by causing blood clots to form.
    In ALL, too many stem cells develop into a type of white blood cell called lymphocytes. These lymphocytes may also be called lymphoblasts or leukemic cells. There are 3 types of lymphocytes:
  • B lymphocytes that make antibodies to help fight infection.
  • T lymphocytes that help B lymphocytes make the antibodies that help fight infection.
  • Natural killer cells that attack cancer cells and viruses.
    In ALL, the lymphocytes are not able to fight infection very well. Also, as the number of lymphocytes increases in the blood and bone marrow, there is less room for healthy white blood cells, red blood cells, and platelets. This may cause infection, anemia, and easy bleeding. The cancer can also spread to the central nervous system (brain and spinal cord)."
  •  
    Clinics and Pathology
    Disease ALL
    Prognosis The prognosis (chance of recovery) and treatment options depend on the following:
  • The age of the patient.
  • Whether the cancer has spread to the brain or spinal cord.
  • Whether the Philadelphia chromosome is present.
  • Whether the cancer has been treated before or has recurred (come back).
  •  
    Related Genes
    Gene Symbol BCR
    Description From cancer gene census of CGP:
     
    Gene Symbol EWSR1
    Description From cancer gene census of CGP:
     
    Gene Symbol TFPT
    Description From cancer gene census of CGP, OMIM
     
    Gene Symbol BCL9
    Description From cancer gene census of CGP:
     
    Gene Symbol MLLT7
    Description From cancer gene census of CGP:
     
    Gene Symbol MLLT4
    Description From cancer gene census of CGP:
     
    Gene Symbol MLLT6
    Description From cancer gene census of CGP:
     
    Gene Symbol ABL1
    Description From cancer gene census of CGP:
     
    Gene Symbol ZNF384
    Description From cancer gene census of CGP:
     
    Gene Symbol FOXO3A
    Description From OMIM: "Chromosomal translocations involving band 11q23 occur in various leukemias (see 600328). Most of these translocations result in the fusion of the MLL gene (159555) on 11q23 to a partner gene on one of several other chromosomes. Hillion et al. (1997) characterized a t(6;11)(q21;q23) translocation in a patient with secondary acute leukemia. They found that the MLL gene was fused to a partner gene that they named AF6q21, resulting in chimeric MLL-AF6q21 transcripts. The authors isolated cDNAs encoding AF6q21 from a K562 erythroleukemia cell line. The predicted 403-amino acid AF6q21 protein contains a forkhead domain"
     
    Gene Symbol AF1Q
    Description From cancer gene census of CGP:
     
    Gene Symbol MLL
    Description From cancer gene census of CGP, OMIM
     
    Gene Symbol ABCC1
    Description From OMIM: Grant et al. (1997) located the MRP1 gene close to the short arm breakpoint of the pericentric inversion associated with the M4Eo subclass of acute myeloid leukemia and on the telomeric side of the MYH11 gene (160745).
     
    Gene Symbol AF9
    Description From cancer gene census of CGP:
     
    Gene Symbol AF5Q31
    Description From cancer gene census of CGP:
     
    Gene Symbol PBX1
    Description From cancer gene census of CGP:
     
    Gene Symbol AF4
    Description From cancer gene census of CGP:
     
    Gene Symbol AF3P21
    Description From cancer gene census of CGP:
     
    Gene Symbol EPS15
    Description From cancer gene census of CGP:
     
    Gene Symbol MLLT10
    Description From cancer gene census of CGP:
     
    Gene Symbol MLLT1
    Description From cancer gene census of CGP:
     
    Gene Symbol SEP15
    Description From OMIM: "Megonigal et al. (1998) examined the MLL (159555) genomic translocation breakpoint in acute myeloid leukemia of infant twins. Southern blot analysis showed 2 identical MLL gene rearrangements indicating chromosomal translocation. The rearrangements were detected in the second twin before signs of clinical disease and the intensity relative to the normal fragment indicated that the translocation was not constitutional. Fluorescence in situ hybridization with an MLL-specific probe and karyotype analyses suggested that a t(11;22)(q23;q11.2) disrupted MLL. Known 5-prime sequence from MLL but unknown 3-prime sequence from 22q11.2 formed the breakpoint junction on the derivative chromosome 11, der(11)."
     
    Gene Symbol RUNX1T1
    Description From OMIM: "Linggi et al. (2002) identified the p14(ARF) tumor suppressor (600160), a mediator of the p53 oncogene (191170) checkpoint, as a direct transcriptional target of AML1-ETO. AML1-ETO repressed the p14(ARF) promoter and reduced endogenous levels of p14(ARF) expression in multiple cell types. In contrast, AML1 stimulated p14(ARF) expression and induced phenotypes consistent with cellular senescence. Chromatin immunoprecipitation assays demonstrated that AML1-ETO was specifically bound to the p14(ARF) promoter. In acute myeloid leukemia samples containing the t(8;21), levels of p14(ARF) mRNA were markedly lower when compared with other acute myeloid leukemias lacking this translocation. Repression of p14(ARF) may explain why p53 is not mutated in t(8;21)-containing leukemias and suggests the p14(ARF) is an important tumor suppressor in a large number of human leukemias."
     
    Gene Symbol FCGR2B
    Description From cancer gene census of CGP:
     
    Gene Symbol VAV1
    Description From OMIM: "By analysis of a rodent-human hybrid DNA panel and by chromosomal in situ hybridization, Martinerie et al. (1990) assigned the VAV locus to 19p13.2-p12. VAV and INSR, the insulin receptor gene (147670), appeared to be closely linked; INSR and VAV migrated together in high molecular weight DNA fragments created with rare cutting restriction enzymes that were subjected to pulsed field gel electrophoresis. It may be worth noting that transcription factor-3 (147141), which has been implicated in acute lymphoblastic leukemia associated with translocations (p1;19), is located at 19p13.3-p13.2. "
     
    Gene Symbol RUNX1
    Description From cancer gene census of CGP:
     
    Gene Symbol HLF
    Description From cancer gene census of CGP:
     
    Gene Symbol TCF3
    Description From cancer gene census of CGP, OMIM
     
    Gene Symbol PICALM
    Description From OMIM: "Bohlander et al. (2000) studied a series of 3 patients with AML, 1 patient with T-ALL, and 2 patients with precursor T lymphoblastic lymphoma. The rearrangements were essentially identical in all. In all 6 patients the breakpoint in CALM was at the 3-prime end of the coding region. Three breakpoints could be identified in AF10. The findings indicated that CALM/AF10 fusions differ only slightly with respect to the portion of AF10 present and that there is no obvious difference between the fusions found in AML patients compared to those found in patients with lymphoid malignancies."
     
    Gene Symbol BAD
    Description From OMIM: "Ranger et al. (2003) reported that Bad-deficient mice lacking both long and short Bad proteins were viable, and most cell types appeared to develop normally. Lymphocytes developed normally with no premalignant hyperplasia, but they displayed subtle abnormalities in proliferation and IgG production. Despite the minimal phenotype, Bad-deficient mice progressed, with aging, to diffuse large B-cell lymphoma of germinal center origin. Exposure of Bad-null mice to sublethal gamma irradiation resulted in an increased incidence of pre-T-cell and pro-/pre-B-cell lymphoblastic leukemia/lymphoma. Thus, proapoptotic BAD suppresses tumorigenesis in the lymphocyte lineage. "
     
    Gene Symbol AFF3
    Description From cancer gene census of CGP:
     
    Gene Symbol EEN
    Description From OMIM: "The MLL gene (159555), the closest human homolog of the Drosophila trithorax gene, undergoes chromosomal translocation with a large number of different partner genes in both acute lymphoid and acute myeloid leukemias. So et al. (1997) identified a novel partner gene, designated EEN by them, that was fused to MLL in a case of acute myeloid leukemia. Since no PCR products were amplified from the patient's DNA when specific primers for 4 common MLL fusion partners were used, So et al. (1997) inferred that MLL in this patient was fused to a novel partner gene sequence. As all characterized MLL fusion genes previously identified had been shown to retain the derivative chromosome 11, the 3-prime RACE (rapid amplification of cDNA ends) method was chosen to isolate the fusion partner of MLL in the patient's leukemic cells. "
     
    Gene Symbol IGH
    Description From cancer gene census of CGP:
     
    Gene Symbol GPHN
    Description From cancer gene census of CGP:
     
    Gene Symbol JAK2
    Description From cancer gene census of CGP:
     
    Gene Symbol TTL
    Description From cancer gene census of CGP:
     
    Gene Symbol ARHGAP26
    Description From OMIM: "Borkhardt et al. (2000) stated that mutual translocations involving 11q23 in acute leukemias had been demonstrated to show fusion between the mixed lineage leukemia (MLL; 159555) gene and a variety of different partner genes to a total of 23. The detection of a unique t(5;11)(q31;q23) in an infant with juvenile myelomonocytic leukemia (607785) and an MLL gene rearrangement provided an opportunity to clone another MLL fusion partner gene. By cloning the breakpoints in this translocation, Borkhardt et al. (2000) recovered a member of the GTPase-activating protein (GAP) family, which they identified as the human homolog of the avian GRAF gene (Hildebrand et al., 1996)."
     
    Gene Symbol IKZF1
    Description From cancer gene census of CGP:
     
    Gene Symbol BCL1
    Description From cancer gene census of CGP:
     
    Gene Symbol FLT3
    Description From cancer gene census of CGP, OMIM
     
    Gene Symbol RANBP17
    Description From cancer gene census of CGP:
     
    Gene Symbol ASTL
    Description From cancer gene census of CGP:
     
    Gene Symbol CDK6
    Description From cancer gene census of CGP:
     
    Bibliography
    Title Archipelago regulates cyclin E levels in Drosophila and is mutated in human cancer cell lines.
    Authors " Moberg, K. H.; Bell, D. W.; Wahrer, D. C. R.; Haber, D. A.; Hariharan, I. K."
    Citations "Nature 413: 311-316, 2001. "
    PubMedID 11565033
     
    Title Analysis of the intron-exon organization of the human multidrug-resistance protein gene (MRP) and alternative splicing of its mRNA.
    Authors Grant, C. E.; Kurz, E. U.; Cole, S. P. C.; Deeley, R. G.
    Citations Genomics 45: 368-378, 1997.
    PubMedID 9344662
     
    Title Identification of a novel molecular partner of the E2A gene in childhood leukemia.
    Authors "Brambillasca, F.; Mosna, G.; Colombo, M.; Rivolta, A.; Caslini, C.; Minuzzo, M.; Giudici, G.; Mizzi, L.; Biondi, A.; Privitera, E."
    Citations "Leukemia 13: 369-375, 1999."
    PubMedID 10086727
     
    Title EEN encodes for a member of a new family of proteins containing an Src homology 3 domain and is the third gene located on chromosome 19p13 that fuses to MLL in human leukemia.
    Authors " So, C. W.; Caldas, C.; Liu, M.-M.; Chen, S.-J.; Huang, Q.-H.; Gu, L.-J.; Sham, M. H.; Wiedemann, L. M.; Chan, L. C. "
    Citations "Proc. Nat. Acad. Sci. 94: 2563-2568, 1997.
    PubMedID 9122235
     
    Title Bad-deficient mice develop diffuse large B cell lymphoma.
    Authors "Ranger, A. M.; Zha, J.; Harada, H.; Datta, S. R.; Danial, N. N.; Gilmore, A. P.; Kutok, J. L.; Le Beau, M. M.; Greenberg, M. E.; Korsmeyer, S. J."
    Citations "Proc. Nat. Acad. Sci. 100: 9324-9329, 2003.
    PubMedID 12876200
     
    Title FLT3 mutations in myeloid sarcoma.
    Authors " Ansari-Lari, M. A.; Yang, C.-F.; Tinawi-Aljundi, R.; Cooper, L.; Long, P.; Allan, R. H.; Borowitz, M. J.; Berg, K. D.; Murphy, K. M."
    Citations "Brit. J. Haemat. 126: 785-791, 2004.
    PubMedID 15352981
     
    Title t(11;22)(q23;q11.2) in acute myeloid leukemia of infant twins fuses MLL with hCDCrel, a cell division cycle gene in the genomic region of deletion in DiGeorge and velocardiofacial syndromes.
    Authors Megonigal, M. D.; Rappaport, E. F.; Jones, D. H.; Williams, T. M.; Lovett, B. D.; Kelly, K. M.; Lerou, P. H.; Moulton, T.; Budarf, M. L.; Felix, C. A.
    Citations "Proc. Nat. Acad. Sci. 95: 6413-6418, 1998."
    PubMedID 9600980
     
    Title "The t(8;21) fusion protein, AML1-ETO, specifically represses the transcription of the p14(ARF) tumor suppressor in acute myeloid leukemia."
    Authors "Linggi, B.; Muller-Tidow, C.; van de Locht, L.; Hu, M.; Nip, J.; Serve, H.; Berdel, W. E.; van der Reijden, B.; Quelle, D. E.; Rowley, J. D.; Cleveland, J.; Jansen, J. H.; Pandolfi, P. P.; Hiebert, S. W."
    Citations "Nature Med. 8: 743-750, 2002. "
    PubMedID 12091906
     
    Title The human VAV proto-oncogene maps to chromosome region 19p12-19p13.2.
    Authors "Martinerie, C.; Cannizzaro, L. A.; Croce, C. M.; Huebner, K.; Katzav, S.; Barbacid, M."
    Citations "Hum. Genet. 86: 65-68, 1990."
    PubMedID 2253939
     
    Title "Molecular analysis of the CALM/AF10 fusion: identical rearrangements in acute myeloid leukemia, acute lymphoblastic leukemia and malignant lymphoma patients. "
    Authors "Bohlander, S. K.; Muschinsky, V.; Schrader, K.; Siebert, R.; Schlegelberger, B.; Harder, L.; Schemmel, V.; Fonatsch, C.; Ludwig, W.-D.; Hiddemann, W.; Dreyling, M. H."
    Citations "Leukemia 14: 93-99, 2000. "
    PubMedID 10637482
     
    Title AF6q21, a novel partner of the MLL gene in t(6;11)(q21;q23), defines a forkhead transcriptional factor subfamily.
    Authors Hillion, J.; Le Coniat, M.; Jonveaux, P.; Berger, R.; Bernard, O. A.
    Citations Blood 90: 3714-3719, 1997.
    PubMedID 9345057
     
    Title The human GRAF gene is fused to MLL in a unique t(5;11)(q31;q23) and both alleles are disrupted in three cases of myelodysplastic syndrome/acute myeloid leukemia with a deletion 5q.
    Authors Borkhardt, A.; Bojesen, S.; Haas, O. A.; Fuchs, U.; Bartelheimer, D.; Loncarevic, I. F.; Bohle, R. M.; Harbott, J.; Repp, R.; Jaeger, U.; Viehmann, S.; Henn, T.; Korth, P.; Scharr, D.; Lampert, F.
    Citations Proc. Nat. Acad. Sci. 97: 9168-9173, 2000.
    PubMedID 10908648
     
    Source and Citation
    Source NCI
    Citation "NCI, URL:http://www.cancer.gov/cancertopics/types/leukemia"
    URL http://www.cancer.gov/cancertopics/types/leukemia