Expression pattern of HOXB6 homeobox gene in myelomonocytic differentiation and acute myeloid leukemia

Abstract

Homeobox genes encode transcription factors known to be important morphogenic regulators during embryonic development. An increasing body of work implies a role for homeobox genes in both hematopoiesis and leukemogenesis. In the present study we have analyzed the role of the homeobox gene, HOXB6, in the program of differentiation of the myeloid cell lines, NB4 and HL60. HOXB6 expression is transiently induced during normal granulocytopoiesis and monocytopoiesis, with an initial induction during the early phases of differentiation, followed by a blockade of expression at early maturation. The enforced expression of HOXB6 in promyelocytic NB4 cells or in myeloblastic HL60 cells elicited inhibition of the granulocytic or monocytic maturation, respectively. Furthermore, HOXB6 was frequently expressed (18 out of 49 cases) in AMLs lacking major translocations while it was expressed at very low frequency (two out of 47 cases) in AMLs characterized by PML/RAR-␣, AML-1/ETO, CBF␤/MYH11 fusion and rearrangements of the MLL gene at 11q23. According to these observations, we suggest that a regulated pattern of HOXB6 expression is required for normal granulopoiesis and monocytopoiesis. Abnormalities of the HOXB6 expression may contribute to the development of the leukemic phenotype.

Pediatric acute myeloid leukemia with NPM1 mutations is characterized by a gene expression profile with dysregulated HOX gene expression distinct from MLL-rearranged leukemias

“…Overexpression of HOXB6 in murine bone marrow immortalizes a myelomonocytic precursor and results in AML in vivo, the latency of which is reduced with MEIS1 coexpression. 49 Moreover, HOXB6 is selectively expressed in CD34 À cells, 42,50 and it is interesting to note that cases of NPM1-mutated AML are commonly of myelomonocytic or monocytic morphology, and lack CD34 expression. Recent data suggesting that NPM1-mutated AML is derived from a common myeloid or earlier progenitor are compatible with these observations.…”

Hmgb3: an HMG-box family member expressed in primitive hematopoietic cells that inhibits myeloid and B-cell differentiation

“…Enforced expression of HOXB6, HOXB7, and HOXB8 in hematopoietic cell lines has been shown to block myeloid differentiation. [30][31][32][33] We propose that Hmgb3 overexpression may enhance recruitment of these Hox proteins to their cognate binding sites. HoxB6 expression has been demonstrated to play a role in erythropoiesis and the regulation of early erythrocyte progenitors.…”

The role of HOXB2 and HOXB3 in acute myeloid leukemia

“…HOXA family genes have been thoroughly studied in respect to AML [5][6][7]. While some studies suggest that HOXB family genes are upregulated in certain types of AML, their roles in AML have not yet been defined [8][9][10][11][12][13]. A recent report suggests that HOXB4 expression is elevated in a group of AML patients and higher HOXB4 expression correlated with better prognosis [8].…”

“…A recent report suggests that HOXB4 expression is elevated in a group of AML patients and higher HOXB4 expression correlated with better prognosis [8]. Another report suggests that over-expression of HOXB6 in NB4 cells or in HL60 cells caused inhibition of the granulocytic and monocytic maturation, respectively [12].…”