Crlf2 Antibodies

Cytokine receptor-like factor 2 (Crlf2)

Receptor for thymic stromal lymphopoietin (TSLP). Forms a functional complex with TSLP and IL7R which is capable of stimulating cell proliferation through activation of STAT3 and STAT5.

Also activates JAK2. Implicated in the development of the hematopoietic system.

Gene Information

Mouse
Gene Name:	Crlf2
Uniprot:	Q8CII9
Entrez:	57914

Family

Belongs to:
type I cytokine receptor family

Alternative Names

CRL2; CRL2cytokine receptor CRL2 precusor; CRLF2; CRLF2Y; CRLM-2; Cytokine receptor-like 2; cytokine receptor-like factor 2; ILXR; IL-XR; P2RY8/CRLF2 fusion; PCOR1; Thymic stromal lymphopoietin protein receptor; thymic stromal lymphopoietin receptor; thymic stromal-derived lymphopoietin receptor; TSLP R; TSLP receptor; TSLPR

Molecular Weight

Mass (kDA):
37.762 kDA

Genomic Context

Mouse
Location:	5|5 F
Sequence:	5;

Tissue Specificity

High level of expression in liver, lung and testis. Also expressed in heart, brain, spleen, thymus and bone marrow. Highly expressed in progenitors and myeloid cells. Isoform 2 is expressed in primary hemotopoietic cells.

Diseases

• Leukemia
• Acute Lymphocytic Leukemia
• Inflammation
• Asthma
• Precursor B-cell Lymphoblastic Leukemia-lymphoma
• Dermatitis, Atopic
• Dermatitis
• Down Syndrome
• Chromosomal Translocation
• Janiceps
• Malignant Neoplasms
• L1 Acute Lymphoblastic Leukemia
• Allergy

• Cytogenetic Abnormality
• Leukemogenesis
• Cell Transformation, Neoplastic
• Polyps
• Allergic Asthma
• Nasal Polyps
• Neoplasm, Residual

Pathways

• Pathogenesis
• Cell Proliferation
• Cytokine Production
• Immune Response
• Cell Development
• T Cell Homeostasis
• Localization
• Cell Adhesion
• Cell Activation
• Cytokine Secretion
• Inflammatory Response
• Sensitization
• Notch Signaling Pathway

• Secretion
• Transport
• Thymic Stromal Lymphopoietin Production
• Neurogenesis
• Mast Cell Activation
• Cell Cycle
• T Cell Proliferation

PTMs

• Phosphorylation

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/Crlf2

Best Uses of the CRLF2 Marker

The CRLF2 marker is one of the non-specific markers for leukemia that have been linked with poor prognosis. It could be a potential target for therapeutic intervention. This article will describe how the CRLF2 marker can be used to identify potential therapeutic targets of CRLF2-HighALL. Let's explore some of the best uses of this marker and how it may be used to aid in the treatment of leukemia.

It is a non-specific indicator of leukemia

The transcriptional signature of CRLF2 is of B-ALL. It has been linked to numerous malignancies. It is also sensitive to inhibitors of small molecules of JAKs as well as protein kinase family kinases. Moreover, its recognition as a major aspect of B-ALL has significant diagnostic, prognostic, as well as therapeutic implications.

A mutation in CRLF2 results in the overexpression of the gene within a subset leukemia. CRLF2 overexpression could be caused by various causes, including translocation of CRLF2 to an unrelated chromosome or point mutation at position 232C. The presence of CRLF2 changes is more prevalent in high-risk ALL patients, individuals of Hispanic or Latino ethnicity, and people who suffer from Down syndrome.

The study showed that CRLF2 expression is elevated in patients suffering from B–ALL, including Ph-like B–ALL. In addition the gene is connected to BCR-ABL1 mutations found in these patients and flow cytometry analysis can quickly identify CRLF2 expression. The JAK2 mutation is common in B-ALLs with CRLF2 overexpression and patients with this mutation may benefit from JAK2 inhibitor therapy. Though it was believed previously that they were mutually exclusive, new evidence suggests that CRLF2 and BCR-ABL1 rearrangements may be rare exceptions.

The mutation of CRLF2 in the TCR gene results in the dimerization of CRLF2 and its interaction with JAK2. This results in a higher level of CRLF2 expression as well as the JAK2 gene. This results in a benefit for cells in the absence of cytokines. are absent. Another mutation of CRLF2 is inhibited in leukemia. This mutation in JAK2 increases CRLF2 dimerization in a constant manner and leads to an increase in leukocytes.

Despite its obscure recognition signal sequences, CRLF2 appears to be a non-specific indicator of leukaemia. This translocation involves CRLF2's centromeric region. Similar to this Mullighan et al. identified the CRLF2 gene as having P2RY8. These were not the only findings. IKZF1 encodes IKAROS, the lymphoid differentiation factor.

It is associated with a poor prognosis

Recently, we reported that patients with T-cell lymphoma are more likely have a less favorable prognosis if they have high levels of CRLF2. In 92 consecutive cases, we identified patients with elevated expression of CRLF2. Patients with elevated levels this protein had lower survival rates and EFS as well as lower CIR. In addition, these patients had a 2.5-fold higher risk of relapse.

Previous studies have also shown that overexpression of CRLF2 is associated with a poor prognosis. In actual fact, we observed that overexpression of CRLF2 is associated with a poorer prognosis for children suffering from ALL. This could be due the fact that CRLF2 expression is linked to cells that are not properly controlled. Patients with T-cell ALL are more likely to have CRLF2 overexpression.

In addition to influencing gene expression, CRLF2 also has the potential to influence cell migration and invasion. In fact, inhibiting the expression of CRLF2 in B-ALL decreases cell viability and encourages Apoptosis. A majority of ALL patients had abnormal activation of AKT/mTOR pathways. These findings could be of clinical significance in predicting prognosis, or in responding to therapy.

Many studies suggest that the overexpression of CRLF2 has a negative impact on the patient's outcome in T-ALL. These findings support the need for alternative therapies that target JAK/STAT5 signaling pathways. These findings are encouraging however, more research is required. This research will determine if CRLF2 is a useful prognostic marker in HR T-ALL.

Despite its link to a poor prognosis, CRLF2 remains an underexpressed gene among young patients with B–ALL. However, these patients often have concurrent JAK and PDGFR mutations. Patients with high CRLF2 expression of NRAS or PDGFR have a higher risk of developing cancer. However, the union of these two genes is linked to a poor prognosis.

Patients with high CRLF2 levels were more often PPR. Patients with low CRLF2 were not considered poor prednisone responseers. PCR-MRD did not show a correlation between CRLF2 expression and PCR-MRD. However patients with high CRLF2 expression had a greater risk of developing PPR as compared to patients with normal or low levels. Also, while it has been suggested that CRLF2 expression is linked to poor prognosis, the findings remain unconfirmed.

It could be a potential candidate for therapeutic treatment

Four independent studies have discovered an over-regulation of 50 percent of the CRLF2 gene in BCR-ABL1-like ALL. CRLF2 is a cytokine receptor-like 2 factor, also referred to as thymic lymphopoietin. The T-lymphoid-related factor CRLF2 regulates the development dendritic cell differentiation and inflammation, allergic responses, and B-cell precursor proliferation and survival.

The CRLF2-rearranged ALL subtype has one of the most devastating outcomes among ALL patients. Existing medications that block the JAKSTAT pathway are only moderately effective for patients suffering from CRLF2-rearranged ALL. New treatments are urgently needed. A promising approach is proteolysis-targeting chimeras (PROTAC molecules), which redirect normal cell processes to destroy abnormally active proteins in cancer cells. PROTAC molecules are also being tested in test tubes containing CRLF2-rearranged ALL.

Recent studies have identified a CRLF2 mutation as a biomarker for leukemia. CRLF2 rearrangements include translocation into the immunoglobulin heavy chain locus located on 14q chromosome, PAR1 deletion, and a missense mutation in exon 6 (F232C). Full-length CRLF2 is expressed in leukemic cell lines as a surface marker. The gene expression pattern of these cells is extremely similar to those of Ph-like ALL which is distinguished by gene expression patterns similar to those of the Philadelphia chromosome. Additionally Ph-like ALL is distinguished by an abnormally high growth rate of the cell, genetic mutations, and a variety of other characteristics.

Additionally it is believed that the CRLF2 F232C activating mutation can be targeted by pharmacological agents. HMGN1 is also a key factor in the DS-ALL cell proliferation. The overexpression of this gene may be used to induce cytokine independence. While the results were encouraging but more research is needed to confirm this hypothesis in humans.

It is a non-specific identifier of leukemia

CRLF2 is a new marker for leukemia that can identify the genetic causes of the disease. These genes have been implicated in a variety of cancers of the hematology, including B-ALL. It is not clear whether they specifically act on B-ALL that is CRLF2-overexpressing. Certain have been identified as possible therapeutic targets. These regulators will be studied by researchers in the near future to determine their roles in CRLF2-overexpression.

The exons of the gene code for the extracellular and transmembrane domains. Researchers developed a mutational screening to find single nucleotide polymorphisms within the gene to determine the function of the gene. These were V136M, P122P and were detected in the cell lines of MHH-CALL-4 patients with cancer and MUTZ5.

Patients with B-ALL are more likely to have refractory or relapsed forms of leukemia when they have an elevated level CRLF2. Overexpression of CRLF2 may trigger activation of JAKSTAT, which is the cause of many toxicities in these patients. TKIs aren't the only options. CAR T cells that target CRLF2 may also be an option for eradication or control of leukemia. However, further research is required to determine the exact mechanism controlling CRLF2 expression.

Through the use of ATAC-seq to construct a transcriptional regulatory system enriched in patients with high CRLF2 expression was constructed. This network enabled the discovery of new therapeutic targets. The analysis revealed the overexpression of CRLF2 in patients with B-ALL as associated with changes in gene expression. In addition to identifying these genes, the network analysis uncovered other genes that were related to B-ALL.

Moreover, CRLF2 overexpression can affect the growth of primary lymphoid precursors. To stop the proliferation of these cells, cytokines were introduced into the culture medium in order to promote differentiation to pre-B cells. The culture resulted in 95% CD43+/B220+ cells, with only a few CD13+ myeloid cells. The cells that express CRLF had significantly larger colonies than those of control cells, and these differences were the same across all three platings.

ShRNA was used to reduce CRLF2 expression in a MUTZ5 line of cells. The shRNA plasmid reduced protein expression, allowing the cells to grow at a slower rate. They were not able to completely transform primary cells. This indicates that CRLF2 does not represent any specific marker for leukemia.