Mutations at the SALL4 locus on chromosome 20 result in a range of clinically overlapping phenotypes, including Okihiro syndrome, Holt-Oram syndrome, acro-renal-ocular syndrome, and patients previously reported to represent thalidomide embryopathy

Kohlhase, Jürgen; Schubert, L; Liebers, Manuela; Rauch, Anita; Becker, Kristin; Mohammed, S N; Newbury‐Ecob, Ruth; Reardon, William

doi:10.1136/jmg.40.7.473

Cited by 167 publications

(133 citation statements)

References 25 publications

Supporting

Mentioning

126

Contrasting

Unclassified

Order By: Relevance

“…Like other SALL genes, SALL4 plays an important role in human development, with heterozygous mutations of SALL4 leading to Duane radial ray syndrome. 16,17,21 Its role in hematopoiesis is not completely understood. As revealed in this study, SALL4 is only expressed in CD34 þ hematopoietic stem/progenitor cells, but not mature myeloid or lymphoid cells.…”

Section: Discussionmentioning

confidence: 99%

“…[15][16][17][18][19] Human SALL4 mutations are associated with Duane radial ray syndrome (or Okihiro syndrome). 3,[20][21][22] Duane radial ray syndrome is a human autosomal-dominant syndrome involving radialsided hand anomalies in association with Duane syndrome. Duane syndrome is characterized by an eye movement disorder (strabismus) in which eye abduction, or adduction, or both, is limited.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Differential expression of the novel oncogene, SALL4, in lymphoma, plasma cell myeloma, and acute lymphoblastic leukemia

Cui

Kong

Ma³

et al. 2006

Modern Pathology

View full text Add to dashboard Cite

CanadaSALL4, a newly identified zinc-finger transcriptional factor important for embryonic development, is mapped to chromosome 20q13. Previously, we reported that SALL4 was constitutively expressed in acute myeloid leukemia and SALL4 transgenic mice developed acute myeloid leukemia. In this study, we aimed to survey SALL4 protein expression in benign and neoplastic hematopoietic tissues in addition to acute myeloid leukemia using immunostaining with a polyclonal anti-SALL4 antibody. Primary hematological tumors (178) and 15 benign hematopoietic tissues were examined. Reverse transcription-polymerase chain reaction was also performed to detect SALL4 mRNA expression on eight precursor B-cell lymphoblastic leukemia/lymphomas, 10 benign hematopoietic tissues, and seven hematopoietic cancer cell lines. Of the benign tissues, SALL4 expression was detectable only in CD34 þ hematopoietic stem/progenitor cells (2/2 at protein level, 3/3 at RNA level). In neoplastic tissues, only precursor B-cell lymphoblastic leukemia/lymphomas had detectable SALL4 (12/16 at protein level, 7/8 at RNA level), similar to that observed in acute myeloid leukemia. Of the seven cell lines examined, only those derived from acute myeloid leukemia and precursor B-cell lymphoblastic leukemia/ lymphomas were positive. To conclude, SALL4 expression is normally restricted to CD34 þ hematopoietic stem/ progenitor cells. The persistence of SALL4 expression in leukemic blasts in precursor B-cell lymphoblastic leukemia/lymphomas resembles to what we observed in acute myeloid leukemia, and correlates with the maturation arrest of these cells. We have shown in our previous study that the constitutive expression of SALL4 in mice can lead to acute myeloid leukemia development. The similar expression pattern of SALL4 in acute myeloid leukemia and B-cell lymphoblastic leukemia/lymphomas suggests that these two disease entities may share similar biological features and/or mechanisms of leukemogenesis. More definite studies to investigate the role of SALL4 in the pathogenesis of B-cell lymphoblastic leukemia/lymphomas are needed in the future to address this question.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Differential expression of the novel oncogene, SALL4, in lymphoma, plasma cell myeloma, and acute lymphoblastic leukemia

Cui

Kong

Ma³

et al. 2006

Modern Pathology

View full text Add to dashboard Cite

show abstract

“…In humans, the SALL gene family is involved in normal development, as well as in tumorigenesis. [126][127][128][129][130][131][132] During normal hematopoiesis SALL4 isoforms are expressed in the CD34 þ hematopoietic stem and progenitor cell population, and they are rapidly turned off (SALL4B), respectively, downregulated (SALL4A) in normal human bone marrow and peripheral blood. 125 SALL4 isoforms were constitutively expressed on the mRNA and the protein level in all primary human AML samples tested, as well as in all AML cell lines.…”

Section: Other Mechanisms Of Aberrant Wnt Signaling In Amlmentioning

confidence: 99%

The emerging role of Wnt signaling in the pathogenesis of acute myeloid leukemia

Steffen

Berdel

et al. 2007

Leukemia

View full text Add to dashboard Cite

Wnt signaling plays an important role in stem cell self-renewal and proliferation. Aberrant activation of Wnt signaling and its downstream targets are intimately linked with several types of cancer with colon cancer being the best-studied example. However, recent results also suggest an important role of Wnt signaling in normal as well as leukemic hematopoietic stem cells. Aberrant activation of Wnt signaling and downstream effectors has been demonstrated in acute myeloid leukemia. Here, mutant receptor tyrosine kinases, such as Flt3 and chimeric transcription factors such as promyelocytic leukemia-retinoic acid receptor-a and acute myeloid leukemia1-ETO, induce downstream Wnt signaling events. These findings suggest that the Wnt signaling pathway is an important target in several leukemogenic pathways and may provide a novel opportunity for targeting leukemic stem cells.

show abstract

“…It is unclear at present whether these conditions are truly distinct or whether several overlap syndromes exist [15]. It has been reported that patients with typical radial ray malformations with Duane syndrome might carry a SALL4 mutation, region of chromosome 20 [16]. However, the clinical manifestations of Holt-Oram syndrome vary, and range from subclinical radiographic findings to overt, life-threatening disease.…”

Section: Discussionmentioning

confidence: 99%

A Case of Malignant Pheochromocytoma with Holt-Oram Syndrome

et al. 2008

View full text Add to dashboard Cite

Abstract.A 23-year-old female patient with malignant pheochromocytoma was admitted to the Tokyo Women's Medical University. The patient had been clinically diagnosed with Holt-Oram syndrome at birth. Since she had complex congenital heart disease, chronic heart failure, and severe hypoxia, the risk surrounding surgery to remove the primary tumor was predicted to be very high, and subsequently, chemotherapy was performed. The patient was not able to continue chemotherapy due to adverse effects. However, for one year, both her hypertension and catecholaminedependent symptoms were well controlled by an alpha-adrenergic and beta-adrenergic receptor blockade, although the patient did experience high plasma norepinephrine levels. To our knowledge, this is the first report of a patient with the combination of malignant pheochromocytoma and Holt-Oram syndrome. A correlation between chronic hypoxia and pheochromocytoma has been reported. This instructive case reminds us to consider the possibility of pheochromocytoma with congenital heart disease when these types of unexpected or unusual symptoms are encountered.

show abstract

Mutations at the SALL4 locus on chromosome 20 result in a range of clinically overlapping phenotypes, including Okihiro syndrome, Holt-Oram syndrome, acro-renal-ocular syndrome, and patients previously reported to represent thalidomide embryopathy

Cited by 167 publications

References 25 publications

Differential expression of the novel oncogene, SALL4, in lymphoma, plasma cell myeloma, and acute lymphoblastic leukemia

Differential expression of the novel oncogene, SALL4, in lymphoma, plasma cell myeloma, and acute lymphoblastic leukemia

The emerging role of Wnt signaling in the pathogenesis of acute myeloid leukemia

A Case of Malignant Pheochromocytoma with Holt-Oram Syndrome

Contact Info

Product

Resources

About